Cancer Research and Treatment

Volume 30(5); October 1998

Original Articles

Expression of EGF Receptor Family Genes and Proteins in Gastric Cacner ( EGFR , c-erbB-2 , c-erbB-3 , c-erbB-4 ): Hae Wan Lee, Eun Young Choi, Chang Dae Bae, Han Kwang Yang, Woo Ho Kim, Jin Pok Kim; J Korean Cancer Assoc. 1998;30(5):853-868.

Abstract PDF: PURPOSE
to evaluate the relationship between the expression of EGF receptor gene family and clinico-pathologic parameters.
MATERIALS AND METHODS
We compared adenocarcinoma tissue with normal mucosa obtained from same patients in 60 cases. The amplifications of DNA was examined by slot blot, while the expression of mRNA by ribonuclease protection assay, and that of protein by immunohistochemistry.
RESULTS
Expression of EGFR mRNA was observed in 9 of 59, that of c-erbB-2 mRNA in 8 of 57, that of c-erbB-3 mRNA in 4 of 60, and that of c-erbB-4 mRNA in 13 of 59. The expression of EGFR in expanding type showed a higher tendency than that in infiltrative type. The expression of c-erbB-2 in poorly differentiated adenocarcinoma showed a higher tendency than that in well differentiated adenocarcinoma. And expression of c-erbB-2 was correlated with presence of endolymphatic tumor emboli. No significant correlation was observed between expression of EGFR mRNA and that of its protein or amplification of its DNA. Similarly, No clear relationship between c-erbB-2 gene amplification and expression of mRNA or proteins was detected.
CONCLUSION
EGFR, c-erbB-2, c-erbB-3, and c-erbB-4 were expressed in gastric adenocarcinoma in Korea. The presence of EGF receptor gene family by various tumor cells suggested that it may play an important role in adenocarcinoma. Therefore further studies are currently being carried out to clarify the role of these oncogenes in tumor behavior and gastric carcinogenesis.

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Prognostic Value of CEA and CA19 - 9 in Serum and Peritoneal Washing Fluid in Gastric Carcinoma: Sang Uk Han, Yong Kwan Cho, Seong Woo Hong, Young Ae Lim, Yun Sik Kwak, Myung Wook Kim; J Korean Cancer Assoc. 1998;30(5):869-878.

Abstract PDF: PURPOSE
The clinical significance of preoperative serum levels of CEA and CA19-9, levels of CEA and CA19-9 in peritoneal washing fluid and free cancer cells in peritoneal washing fluid in gastric cancer patients were evaluated in this study.
MATERIALS AND METHODS
Serum and peritoneal levels of CEA and CA19-9 and peritoneal washing cytology in 115 patients with gastric cancer were analyzed with respect to the prognostic factors using univariate and multivariate analysis.
RESULTS
Positive rate of serum CEA and CA19-9 was 16.5%, 13.0%. And that of peritoneal washing CEA, CA19-9 and cytology was 15.7%, 7.8% and 9.6%. A univariate analysis showed that tumor markets in serum and peritoneal washing fluid and peritoneal washing cytology had significant correlations with the progression of the tumors, and patients with positive serum or peritoneal tumor markers had poorer survival after operation than did the patients with negative tumor markers. But in a multivariate analysis showed that only peritoneal CA19-9 was an independent risk factor. And combination of these five markers provided rnore predictable prognostic informations in a multivariate analysis.
CONCLUSION
Combination of serum or peritoneal levels of CEA, CA19-9 and washing cytology appeared to be a useful marker for managing gastric cancer patients.

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Clinicopathological Analysis of Female Gastric Cancer - Comparative study according to the sex fo the patients: Jin Pok Kim, Hang Jong Yu, Young Chul Kim, Soo Jin Kim, Joo Ho Lee, Han Kwang Yang; J Korean Cancer Assoc. 1998;30(5):879-885.

Abstract PDF: PURPOSE
The purpose of this study is to evaluate the differences of the clinicopathological features and survival rates in gastric cancer according to the sex of the patients.
MATERIALS AND METHODS
We reviewed 5,784 cases of gastric cancer patients who underwent laparotomy at the Department of Surgery, Seoul National University Hospital fmm Jan. 1986 to Dec. 1995. We have analyzed clinicopathologic features including tumor location, Bonmann type, depth of invasicm, lymph node metastasis, distant metastasis, TNM stage, histologic differentiation and survival rates according to the sex of the patients.
RESULTS
The mean age of female patients was 52.4 years, which is lower than that of male, 54.8 years. There were no differences in tumor location, Borrmann type, depth of invasion, lymph node metastasis, distant metastasis, TNM stage of tumor between male and female. But there were some differences in histologic differentiation; well- and moderately differentiated cancers were more common in male and signet-ring cell cancers were more common in female. Female shows slightly better prognosis than male. But the prognosis of young female was poorer than that of young male.
CONCLUSION
In gastric cancer patients, differences in histologic differentiation and more aggressive nature of the signet-ring cell cancer in female may affect the survival differences according to the sex.

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Clinicopathologic Comparison of the Young and the Old in the Patients with Gastric Cancer: Shin Nam Min, Hyung Rok Kim, Dong Yi Kim, Young Jin Kim, Shin Kon Kim; J Korean Cancer Assoc. 1998;30(5):886-891.

Abstract PDF: PURPOSE
Gastric cancer is considered to be a disease of the middle aged and elderly, but there was increased interest in clinicopathologic features of both the young aged and the old aged gastric cancer.
MATERIALS AND METHODS
In an attempt to compare the young below 35 years old with the old over 70 years old about the clinicopathologic characteristics, we reviewed 110 young patients and 146 old patients who were experienced at the Department of Surgery, Chonnam University Hospital from July 1982 to June 1997. We have analyzed the age, sex ratio, location, size, number of the cancer, Borrmanns classification, histologic classification, stage of the cancer, DNA ploidy, curative resectibility, 5 year survival rate in both groups. Comparisons of outcomes between groups were done using z(2) analysis. P value of <.05 was considered significant. A statistical test of the survival rates was made with the Z test and Kaplan-Meier method. Other statistics were analyzed by the log-rank method.
RESULT
In the old, the incidence af the gastric cancer was higher in man than in woman(2.24: 1). In the young, the male to female sex ratio was 1: 1.16. The antrum was the most common site of gastric cancer in both groups. The cardia was more frequently involved in the young than the old(17.3%:7.5%). In the histologic classification, tubular adenocarcinoma was the most common in both groups. The young had 17.3% of incidence of signet ring cell carcinoma, but 2.7% in the old. The incidence of the early gastric cancer was 20.0% in the young and 17.8% in the old, which was not significantly different. The incidence of Borrmann type III was predominant in both groups. In Borrmann type IV, the young was revealed 18.0%, the old was revealed 8.2%, but there was no significant difference statistically. There were no significant differences in the stage and 5-years survival rate of the gastric cancer in both groups.
CONCLUSION
This study showed the differences between the young and the old in the sex ratio, location, histological types of the gastric cancer. It meaned that there were some differences between the both groups in the etiology of gastric cancer, development and progression patterns.

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Selection of Surgical Procedure in the Elderly with Advanced Gastric Cancer: Hyeoung Joon Kim, Tae Kyung Sohn, Woo Joong Kim, Kyung Suk Chung; J Korean Cancer Assoc. 1998;30(5):892-899.

Abstract PDF: PURPOSE
The quality of life has become increasingly important as an outcome when assessing patients who have had surgery for advanced gastric cancer in the elderly. The purpose of this study was to study the validity of quality of postoperative life as a criterion in the decision-making process as well as the results of operation for advanced gastric cancer in the elderly.
MATERIALS AND METHODS
Spitzer's quality of life index, postoperative mortality and survival were evaluated in 67 patients(over 65 years of age) with advanced gastric cancer who had undergone operation between 1988 and 1997 at the Department of Surgery, Kangnam Sacred Heart Hospital.
RESULTS
The quality of life score and median survival correlated with TNM clinical stage(IIIa; 7.1+/-1.8, 36.0 months vs. IIIb: 5.8+/-2.8, 28.6 months vs. IV: 2.9+/-1.9, 4.5 months), resectability(reseetion: 5.9+/-2.7, 21.0 months vs. no resection: 3.0+/-2.0, 4.0 months), curability(curative operation: 6.5+/-2.4, 29.0 months vs. palliative operation: 3.3+/-2.4, 6.0 months), type of gastrectomy(subtotal gastrectomy: 6.4+/-2.7, 28.0 months vs. totai gastrectomy: 4.5+/-2.6, 9.0 months), but not with age or sex. There was a difference in operative mortality according to age group(65~70 years: 7.8% vs. >70 years: 18.8%), resectability(resection: 7.4% vs. no resection: 23.0%) and curability (curative operation: 2.3% vs. palliative operation: 25.0%).
CONCLUSION
The results suggest that surgical resection offers the only chance for improved survival and qulaity of life. Gastric resection, even with total gastrectomy, can be undertaken to reduce tumor burden, decrease threats of obstruction, hemarrhage, or perforation and improve quality of life in the elderly if there is little coexisting impairment.

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A Phase 2 Trial of PEF ( Cispatin , Etoposide , 5-Fluorouracil ) Chemotherapy for Metastatic Stomach Cancer: Yoon Koo Kang, Kwang Seob Yum, Hee Jun Cho, Jhin Oh Lee, Taik Koo Yun; J Korean Cancer Assoc. 1998;30(5):900-906.

Abstract PDF: PURPOSE
To determine the activity and toxicities of PEF (Cisplatin, Etoposide, 5-Fluorouracil) chemotherapy for stomach cancer.
MATERIALS AND METHODS
Patients with previously untreated metastatic stomach cancer were treated with PEF regimen which consisted of cisplatin (20 mg/m2 i.v. days 1~5), etoposide (100 mg/m2 i.v. days 1, 3, 5), and 5-fluorouracil (5-FU)(800 mg/m2 i.v. infusion for 12 hours days 1~5). Chemotherapy was repeated every 3 weeks until disease progressed or toxicities were intolerable.
RESULTS
Between May 1989 and July 1990, 40 patients were enrolled in this protocol. Twelve patients were lost to follow up after one cycle of chemotherapy and inevaluable. After 2~8 cycles (median 3) of chemotherapy, 20 out of 28 evaluable patients showed objective responses without any complete response, making the response rate 71% (95% confidence interval: 54~89%). The responses lasted from 4+ to 39 weeks (median: 38 weeks). The overall survival of total evaluable patients was 4+ ~50+ weeks (median 38 weeks). Among total 109 cycles of chemotherapy, cycles were delayed or doses were reduced in 48 cycles (44%) because of leukopenia (in 61 cycles: 56%) and/or thrombocytopenia (in 14 cycles: 13%). However, there was no treatment-related death. Nausea/vomiting and alopecia were experienced in most of patients. The stomatitis was experienced in 7 patients (25%) but completely reversible. In contrast, the peripheral neuropathy which developed in 4 patients (14%) after 5 cycles of chemotherapy was not reversible.
CONCLUSION
The PEF regimen was active and tolerable in stomach cancer.

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Cispatin , Etoposide , Leucovorin and 5-Fluorouracil ( PELF ) Combination Chemotherapy for Advanced Gastric cancer: Interim Report: Il Rang Park, Si Young Kim, Jeong Hee Kim, Hwi Joong Yoon, Kyung Sam Cho; J Korean Cancer Assoc. 1998;30(5):907-913.

Abstract PDF: PURPOSE
In attempt to provide a feasible chemotherapeutic regimen for advanced gastric cancer patients, the combination of cisplatin, epirubicin, leucovorin and fluorouracil (PELF) has been developed. A trial was performed to confirm the clinical activity, in terms of response rate and toxicity and duration of survival, of the PELF combination chemotherapy.
MATERIALS AND METHODS
From April 1995 to July 1997, patients with measurable unresectable and/or metastatic gastric cancer received PELF combination chemotherapy. The regimen consisted of cisplatin 40 mg/m2 IV on days 1 and 5; epirubicin 30 mg/m2 IV on days 1 and 5; 5-fluorouracil 300 mg/m2 and leucovorin 20 mg/m2 IV on days 1 through 4. The cycle was repeated every 3 weeks.
RESULT
Among 21 evaluable patients, 1 patient achieved complete response (5.3%) and 8 patients, partial response (42.1%). The median survival of overall patients was 36 weeks, the median time to progression of 21 evaluable patients was 27 weeks. There was severe myelosuppression; leucopenia 73.1%, WHO grade 3~4 11.5% of cycles. Non-hematologic toxicities were also severe nausea or vomiting in 100% of patients, grade 3~4 13.0% of patients, alopecia in 91.3% of patients, grade 3~4 52.2% of patients.
CONCLUSION
This study showed that the PELF combination is effective in overall response rates. However, it is not recommended for routine clinical use because of its toxicities. Further phase III study will be warranted.

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Microsatellite Instability Correlate with a Prognosis in Breast Cancer: Hwa Young Lee, Chengshi Quan, Soo Jung Gong, Joon Oh Park, Joong Bae Ahn, Kwang Yong Shim, Sun Young Rha, Nae Choon Yoo, Woo Ick Yang, Joo Hang Kim, Jae Kyung Roh, Kyong Sik Lee, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(5):914-920.

Abstract PDF: PURPOSE
Microsatellite instability in patients with defects in the mismatch repair system resulting in RER has a high risk of accumulating mutations in oncogene and tumor suppressor gene. In this study, we evaluated the incidence of microsatellite instability in breast cancer by comparing PCR-amplified sequences from frozen samples of normal and tumor tissue fram affected patients. We also investigated whether RER was associated with TGF-beta RII mutation.
MATERIALS AND METHODS
Fifty surgically resected breast cancer specimens from Jan. 1996 to June, 1997 were used for study. Microsatellite instability(referred to as replication error, RER) at three loci with BAT 26, BAT 40, TA10 was analyzed by polymerase chain reaction and the results were compared with clinicopathologic characteristics.
RESULTS
Of the 50 breast cancer patients, 14(28%) were RER(+) at one or more microsatellite loci, and 4(8%) showed TGF-beta RII mutation. Microsatellite instability was significantly correlated with lymph node involvement(especially in case of 4 or more lymph nodes involvement). But we could not find any correlation between RER and other prognostic factors including tumor size, tumor grade, hormone receptor status and pathology. One of fourteen tumors with RER(+) showed TGF-beta RII mutstion. There was no signiticant correlation between RER(+) and TGF-beta type II receptor gene mutation.
CONCLUSION
The findings suggest that microsatellite instability would be useful prognostic factor in unilateral breast cancer patients, and the role of targeting to gene mutation will be explored in future studies.

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A Study on the p53 Mutations in Korean Breast Cancer Tissues: Hong Kyu Baik, Pah Jong Jung, Youl Hee Cho, Young Hyeh Ko; J Korean Cancer Assoc. 1998;30(5):921-934.

Abstract PDF: PURPOSE
The role of mutation of p53 gene on the carcinigenesis was studied since 1991. There were some relationships of p53 mutation and clinicopathologic factors. This sutudy was designed for the clinicopathologic and genetic factor relation in Korean breast cancer.
MATERIALS AND METHOD
A retrospective study on the clinicopathologic findings such as age, menopausal status, TNM stage, histologic grade, estrogen receptor, DNA ploidy and S-phase fraction was camed out on 47 breast cancer tissues which had been resected at the Department of Surgery, Hanyang University Hospital. Forty-seven tissues were grouped into 3 groups. Group 1 was ductal carcinoma in situ, Group 2 was invasive ductal carcinoma without axillary lymph node metastasis and Group 3 was invasive ductal carcinoma with axillary lymph node metastasis. The numbers of tissues in each groups were 14, 15 and 18, respectively. Mutation screening on the p53 tumor suppressor gene was also performed with PCR-SSCP-direct sequencing method from the genomic DNA extracted from formalin fixed and paraffin-embedded pathologic tissue blocks. The results were as followings; RESULT: p53 mutations were detected in 12 cases(25.5%) of 47. In Group 1, 4 cases(28.6%) had mutations, and in Group 2, 5 cases(33.3%), and in Group3, 3 cases(16.7%). There was no significant differences in mutation rate between three groups. In 12 mutations detected, 6 cases were transition, 5 of which were missense mutation in coding sequences, and one of which was splicing mutation at acceptor site. One case was transversion and five cases were deletions or insertions of various lengths resulting in frameshift mutations. There was no statistically significant difference between groups and clinicopathologic factors except the strong relationship between the negative estrogen receptor and p53 mutation(p< 0.001).
CONCLUSIONS
From the above findings, p53 gene could be considered to be inactivated at the all stage of multistep carcinogenesis processes. The nature of mutations and genetic background of Korean breast cancers may be somewhat different from those of Caucasians. And the p53 mutation status may be used as one of the useful prognostic factors in addition to the estrogen receptor status.

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Plasma TGF-beta1 as a Tumor Marker in Breast Cancer Patients: Hwa Young Lee, Sun Young Rah, Soo Jung Gong, Joong Bae Ahn, Kwang Yong Shim, Joon Oh Park, Hyun Ja Kwon, Nae Choon Yoo, Sook Jung Jeong, Hyun Cheol Chung, Joo Hang Kim, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim, Jae Kyung Roh; J Korean Cancer Assoc. 1998;30(5):935-942.

Abstract PDF: PURPOSE
Transforming Growth Factor-beta1(TGF-beta1) is the most potent inhibitor of the progression of normal mammary epithelial cells through the cell cycle. However, advanced breast cancers are mostly refractory to TGF-beta mediated growth inhibition and produce large amounts of TGF-beta, which may enhance tumor cell invasion and metastasis by its effects on extracellular matrix. Yet, little is known about the association of TGF-beta1 with progression of malignant disease in vivo. In this study, we evaluated the preoperative and postoperative plama level of TGF- in breast cancer and analyzed the utility of plasma TGF-beta1 as possible tumor marker.
MATERIALS AND METHODS
ELISA(enzyme-linked immunosorbent assay) was used to measure plasma TGF-beta1 level in 45 newly diagnosed breast cancer patients and in 15 normal healthy people, and the results were compared with clinicopathologic characteristics.
RESULTS
The mean plasma TGF-beta1 levels were 1.73+/-0.47 ng/ml in normal people and 5.05+/-1.41 ng/ml in breast cancer patiens. In 37 operated patients, the preoperative plasma TGF-beta1 level was 6.34+/-1.34 ng/ml and decreased to 4.48+/-1.07 ng/ml in patients with follow-up after surgery and 4.74+/-0.79 ng/ml in patients with chemotherapy. However, there was no significant correlation between plasma TGF-beta1 level and known prognostic factors including tumor size, LN involvement, tumor grade, hormone receptor status, and pathology.
CONCLUSION
These findings suggest that the plasma TGF-g level can be a tumor marker in breast cancer patients and the association with progression of breast cancer will be explored in future studies.

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Clinical Trial

Prognostic Significance of Peritumoral Lymphatic Vassel Invasion in Breast Cancer: Geun Tong Park, Min Gyun Im, Lee Su Kim, Song Kim, Chang Sig Choi, Bong Hwa Lee; J Korean Cancer Assoc. 1998;30(5):943-950.

Abstract PDF: PURPOSE
The well-known prognostic factors for breast cancer, such as axillary lymph node status, do not always account for the exact outcome. The developinent of other accurate prognostic factors would help in assessing high risk for the disease recurrence and death. Recently, there are reports that peritumoral lymphatic vessel invasion is a good prognostic factor to solid tumors in animal studies and clinical trials. This study was performed to estimate the significance of peritumoral lymphatic vessel invasion (PLVI) as a prognostic factor in breast cancer. Also, PLVI was compared with established clinicopathological prognostic factors and hormone receptors.
MATERIALS AND METHODS
A group of patient was selected from the Department of Surgery, College of Medicine, Hallym University, which consists of 43 out of 96 patients who received curative operation from 1985 to 1993. Peritumoral lymphatic vessel invasion by tumor cells on H&E stain was considered PLVI positive. We classified 43 breast-cancer patients into 32 with negative PLVI and ll with positive PLVL. We estimated the correlation between the PLVI and other established prognostic factors. We also calculated survivals based on PLVI.
RESULTS
The 4-year disease-free survival rate was 61.8+/-8.7%, and the 4-year overall survival rate was 73.0+/-8.0%. The receptor status of estrogen and of progesterone had significant impacts on survival (ER: p=0.0001, PR: p=0.0001). Also, metastasis status of lymph node had significant impacts on overall survival (p=0.0148). We found a significant correlation between PLVI and tumor size (p=0.004), estrogen receptor (p=0.002), progesterone receptor (p=0.006), but could not find any significant corelation between PLVI and menopausal status, histologic grade, nuclear grade, lymph node metastasis. PLVI status was corelated with disease free survival rate (p=0.01) and overall survival rate (p=0.01).
CONCLUSION
The determination of PLVI in breast cancer tissue may be useful as a prognostic factor, but it is necessary to investigate the PLVI in a large number of patients before this conclusion can be stated with certainty.

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Original Articles

Effectiveness of Sentinel Node Biopsy in the Prediction of Axillary Nodal Status in 111 Patients with Breast Cancer: Jeong Hyun Yang, Hae Kyung Lee, Seok Jin Nam; J Korean Cancer Assoc. 1998;30(5):951-955.

Abstract PDF: PURPOSE
Recently, results of many trials that intend to decide the axillary status through more conservative procedures are reported. One of these is sentinel node biopsy. This method is regarded as reasonable and selective. Some investigators tend to omit axillary dissection in the patient who is determined to have negative node clinically and negative result in sentinel node biopsy procedure. This study was designed to know how accurate the sentinel node biopsy method can predict axillary nodal status.
MATERIALS AND METHOD
The patients group was selected from Department of Surgery at SMC, consisting of 111 patients with surgically curable breast cancer from Sept. 1995 to Apr. 1997. Isosulfan blue was injected in the center of mass and the margins of 4 quadrant under the general anesthesia. Axillary dissection was done 5 minutes after injection to identify the stained lymphatics. When stained lymphatics were identified, dissection was performed along the lymphatics bidirectionally to detect the stained lymph node nearest to the primary tumor (sentinel node). After frozen biopsy of sentinel node, routine axillary node dissection was performed. Results of frozen biopsy were compared with the final pathologic results.
RESULTS
Sentinel node was detected in 80 of the 111 cases (72.1%) and there were 44 (55.0%) axillary metastasis cases in sentinel node detection group. In 14 of 44 cases, sentinel node was only positive. In 5 of 41, sentinel node were falsely negative for malignancy. Negative predictive value of the method is 87.8% (36/41).
CONCLUSION
Sentinel node biopsy method can predict the axillary nodal status in patients with breast cancer. This method can lead to more conservative treatment, eventually omitting axillary nodal dissection in selected patients.

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Detection and Clinical Significance of Apoptotic Bodies in Laryngeal Squamous Cell Carcinomas: Chan Seung Hwang, Young Ho Hong, Hoon Kim; J Korean Cancer Assoc. 1998;30(5):956-962.

Abstract PDF: PURPOSE
The purpose of this study was to analyze the relationship between apoptotic index and clinicopathological findings in laryngeal squamous cell carcinomas.
MATERIALS AND METHODS
Fourty-one cases of laryngeal squamous cell carcinomas were analyzed for the detection of apoptotic bodies by in situ hybridization.
RESULTS
The average apoptotic index was 9.38+/-2.89. The apoptotic indices were 11.26+/-1.86, 8.17+/-2.55, and 4.32+/-2.41 in well differentiated, moderately differentiated and poorly differentiated carcinoma, respectively. The histopathological differences and apoptotic index were statistically significant(p<0.05). But there was no relationship between apoptotic index and T stage, nodal status, recurrence and treatment results.
CONCLUSION
The apoptotic index was only related to cellular differentiation. Also these results suggest that the numbers of apoptotic bodies in the tumor tissues can make it possible to presume indirectly the malignant potentiality of the tumor and will help us to understand the biologic behavior of head and neck cancer.

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Fine Needle Aspiration Biopsy for Metastatic Cervical Lymphadenopathy: Min Hee Huh, Seong Heum Park, Hee Jin Chang, Jung Il Suh, Kyung Woo Choi; J Korean Cancer Assoc. 1998;30(5):963-969.

Abstract PDF: PURPOSE
This study was intended to evaluate the value of the FNAB in the diagnosis of the suspected metastatic cervical lymphadenopathy.
MATERIALS AND METHODS
221 patients diagnosed as metastatic cervical lymphadenopathy by FNAB from Jan., 1990 to Oct., 1994 were analyzed retrospectively. They represented 92.1% of metstatic cervical lymphadenopathy managed and 15.7% of 1,411 FNAB's performed during the same period. 33 cases with lymphoma were excluded in this study.
RESULTS
In 107 patients with cervical lymphadenopathy who also received confirmatory node biopsy, the sensitivity, specificity, positive and negative predictive values of FNAB for the metastatic cervical lymphaenopathy were 79.3%, 100%, 100% and 44.1% respectively. In 76 (33.4%) patients the histopathologic types of the primary cancers were decided by information gained from FNAB alone. There were two kinds of tendency that GI cancers metastasized to left-sided cervical nodes (88.1%) and breast and lung cancers to ipsilateral supraclavicular nodes in high frequencies (94.1% and 86.8%, respectively). No complications were associated with FNAB.
CONCLUSION
FNAB is a simple, rapid, inexpensive and highly specific diagnostic tool in the evaluation of suspected metastatic cervical lymphadenopathy. The sensitivity and negative predictive value, however, are relatively low. When the clinical findings strongly suggest metastatic lymphadenopathy, the negative FNAB should be followed by confirmatory biopsy. Information gained from it guides further diagnostic and therapeutic plans. Surrounding normal tissues are not damaged, and the theoretical hazards of local implantation of tumor cells and complication are negligible.

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The Expression of TGF-beta1 and TGF-beta2 in Prostatic Carcinoma: Ki Kwon Kim, Jung Ran Kim, Dong Hoon Kim, Tae Jung Jang, Jong Im Lee, Kyung Sub Lee; J Korean Cancer Assoc. 1998;30(5):970-979.

Abstract PDF: Transfonning growth factor-beta (TGP-beta) is a multipotent growth factor affecting development, homeostasis, and tissue repair. We evaluate the significance of the expression of TGF-beta1 and TGF-beta2 and correlation with prognostic factors in prostate cancer.
MATERIALS AND METHODS
In order to investigate the expression of TGF-beta1 and TGF-beta2, we analyzed Immunohistochemical staining from paraffin blocks of 22 cases of the prostate carcinoma and adjacent normal prostate.
RESULTS
The expressions of TGF-beta1 and TGF-beta2 were noted in the cytoplasm of tumor cells, normal epithelial cells and stroma. The staining intensity and areas were examined and scored from 0 to 5. The TGF-beta1 staining scores of the tumor cells were higher than that of the adjacent normal epithelial cells (p=0.001). The TGF-beta2 staining scores of the tumor cells were also higher than that of the adjacent normal epithelial cells (p=0.003). However, there were no correlation between tumor surrounding stroma and normal stroma in TGF-beta1 and TGF-beta2 staining scores. The serum PSA level, the clinical stage, the Gleason score and the lymph node metastasis of the tumor did not correlated with the staining score of TGF-beta1 and TGF-beta2.
CONCLUSION
These results indicate that the prostatic cancer was associated with alteration of TGF-beta1 and TGF-beta2 expression by prostatic epithelial cells which play a role in prostatic carcinogenesis.

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Study on the Expression of E-cadherin and Cathepsin B in the Prostatic Carcinomas with the Evaluation of the Gleason Grade: Mee Young Sol, Jin Sook Lee, Hyo Jeong Chae, Moon Kee Chung; J Korean Cancer Assoc. 1998;30(5):980-989.

Abstract PDF: PURPOSE
The purpose of this study is to evaluate the expression of E-cadherin and cathepsin-B in prostatic carcinomas and correlate with the Gleason grades.
MATERIALS AND METHODS
The expressions of E-cadherin and cathepsin B were examined by the immunohistochemical technic using the antibodies against the E-cadherin and cathepsin B on the paraffin block sections of 56 prostatic carcinomas with evaluation of Gleason grading.
RESULTS
E-cadherin expression in normal epithelium was membranous intercellular expression and those of prostate carcinomas were aberrant expressions such as negative expression or cytoplasmic presentation. The expressivity of the E-cadherin according to the progression of the Gleason grading revealed negative membranous expression and tendency of gradual increase of aberrant expression. The normal prostate and BPH revealed expression of cathepsin B mostly in the basal layers of acini as cytoplasmic reaction and the stromal macrophages and microvessel wall also showed positive expression. The prostatic carcinoma showed cytoplasmic positivity in the cancer cells and the expression rate was increased from Gleason grade 2 to Gleason grade 4. But the Gleason grade 5 tissue revealed decreased or negative expression. The Gleason grade 4, especially in the invasive cells and invasive edges, revealed the most intense and frequent expression of cathepsin B and this findings were consistent with the nonnal function of the cathepsin B as a protease degrading the extracellular matrix proteins.
CONCLUSION
E-cadherin expression was aberrant after Gleason grade 6 related with high histologic grades. It is suggested that the E-cadherin expression could tell the potential cancer progression as a tumor suppression factor. The cathepsin B was most strongly expressed in basal cells of the benign prostatic acini and the cancer nests of Gleason grade 4, which tells the possibility that cathepsin B could be a marker of basocellular differentiation and of assessing stromal invasion of prostatic carcinomas.

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Case Report

Primary Malignant Lymphoma of the Epididymis: A case report of involvement by diffuse large B cell lymphoma: Mi Ja Lee, Keun Hong Kee; J Korean Cancer Assoc. 1998;30(5):990-996.

Abstract PDF: Isolated involvement of the epididymis by malignant lymphoma is very rare and almost invariably is associated with lymphoma in the adjacent testis. To date, there are four case reports of primary epididymal lymphoma. In this case, 74-year-old man presented with a 3 cm, painless left epididymal swelling. Extensive staging work-up showed no evidence of extraepididymal spread. The epididymectomy was performed. The enlarged epididymis was firm and entirely replaced by whitish gray homogenous tumor measuring 1.8x0.9 cm. Microscopically, the tumor revealed an interductal, highly cellular infiltration, distorting the normal epididymal architecture. The lymphomatous infiltrate was polymorphic, though the predominant cell type exhibited a large irregular and vesicular nucleus. In many areas, small reactive lymphocytes, eosinophils, and occasional plasma cells were interspersed among the neoplastic cell population. Mitoses were frequent. The small lymphoid cells focally infiltrate through the wall of some tubules and small veins. A variable pattern of sclerosis was present throughout much of the tumor. Also there were non-specific granulomas. Immunohistochemical staining revealed that the large cel1s were B cells (CD20 positive) and conclusively lambda light chain restriction. The smaller reactive lymphoid cells were composed of a mixture of B cells and T cells (CD3, UCHL-1 positive). The DNA analysis of lymphoma shows a diploidy DNA content. S phase fraction is 21%. To date, the patient, who treated with chemotheraphy, remains well 9 months after diagnosis. Most lymphomas of testis and epididymis occur in older men, have an intermediate or high grade, diffuse histology, disseminate early, and follow an aggressive clinical course. This case is some similar to the conventional most lymphomas of testis and epididymis. But unusual fetures included that the tumor showed only confined to the epididymis and marked sclerosis.

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Original Articles

Role of AP-1 Transcriptional Regulation of Vimentin Gene during 12-O-Tetradecanoylphorbol-13-Acetate Differentiation of HL-60 Cells: Kyu Lim, Jin Hee Kim, Do Won Kweon, Sung Min Kim, Myung Sun Lee, Kyung Ah Yun, Mee Young Son, Jong Il Park, Wan Hee Yoon, Byung Doo Hwang; J Korean Cancer Assoc. 1998;30(5):997-1004.

Abstract PDF: PURPOSE
To gain insight on the role of AP-1 in transcriptional regulation of vimentin gene during differentiation of HL-60 cells by 12-0-tetradecanoylphorbol-13-acetate (TPA), the levels of vimentin mRNA and AP-1 have been investigated with Northern blot hybridization and DNA mobility shift assay.
MATERIALS AND METHODS
HL-60 cells were grown in RPMI 1640 medium supplemented with 10% heat-inactivated fetal calf serum and antibiotics in a humidified 5% CO2 at 37 degree C. Total RNA was prepared by a modification of the method of Karlinsey et al. Northern blot hybridization was performed by the method of Virca et al. EcoRI fragment of pVIM-GEM was used as probe for vimentin mRNA. DNA mobility shift assay was performed by the method of Lim et al. End labeled DNA probe(Upper strand, 5'-CGCTTGATGAGTCAGCCG- 3') for AP-1 binding activity was mixed with nuclear extracts in a 20 microliter reaction volume containing 300 mM KC1, 60 mM HEPES, pH 7.9, 25 mM MgCl2, 1 mM EDTA, 1 mM DTT, 60% glycerol, and 2 microgram of poly[dI-dC].
RESULTS
TPA increased vimentin mRNA levels, with maxima1 stimulation reached at 24 hr. The level of vimentin mRNA was induced in proportion to the concentration of TPA. TPA-induced vimentin mRNA was almost reduced by actinomycin-D pretreatment. TPA- induced stimulation of vimentin gene was completely reduced by staurosporin pretreatment. In DNA mobility shift assay, AP-I newly appeared at 24 hr during TPA- induced differentiation and was almost not detected after the pretreatment of staurosporin.
CONCLUSIONS
These results suggest that the induction of vimentin mRNA during TPA- dependent differentiation in HL-60 cells may be mediated by protein kinases C signal transduction and AP-1 is important to transcriptional regulation.

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TGFbeta1 Effect on Survival of Anticancer Drug - resistant L1210 Sublines: Sung Yong Kim, Kyung Sub Lee, Jae Ryong Kim, Jeong Hee Kim; J Korean Cancer Assoc. 1998;30(5):1005-1013.

Abstract PDF: PURPOSE
The inhibitory effect of TGFbeta1 on survivals of L1210 and anticancer drug- resistant L1210 sublines was investigated and the gene expression of TGFbeta1 in these cells was examined.
MATERIALS AND METHODS
The survivals of L1210, adriamycin-resistant(L1210AdR), vincristine-resistant(L1210VcR) or cisplatin-resistant(L1210Cis) cells were measured by MTT assay after treatment of TGFbeta1. Northern analysis was performed for TGFbeta1 gene expression in L1210, L1210AdR, L1210VcR or L1210Cis.
RESULTS
There was no different survival ratio between two groups, control and TGFbeta1(10 ng/ml) treated groups in L1210 cells. However, the survival ratio of L1210AdR was 59% in TGFbeta1 treated group for 96 hours. The survival ratio of L1210VcR was 61% for 96 hours in TGFbeta1 treated group. The survival ratio of L1210Cis was 40% for 96 hours in TGFbeta1 treated group. Expressions of TGFbeta1 gene in drug-resistant sublines were significantly decreased than that of L1210 cells.
CONCLUSION
Growth of anticancer drug-resistant L1210 sublines were inhibited by TGFbeta1 but not in L1210 cells. So, it is suggested that TGFbeta1 gene expression may have a part in anticancer drug-resistance.

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Leukemic Red Marrow Changes Assessed by Proton Magnetic Resonance Spectroscopy Before and Following Chemotherapy: Dong Gun Shin, Hoon Chung, Jong Ki Kim, Young Hwan Rhee; J Korean Cancer Assoc. 1998;30(5):1014-1020.

Abstract PDF: PURPOSE
The purpose of this study was to investigate the possibilities for serial in vivo localized proton magnetic resonance spectroscopy (MRS) examination of bone marrow in patients with acute le,ukemia.
MATERIALS AND METHODS
Selective measurements of the relaxation times Tl and T2 for the water and fat resonance in the bone marrow spectra were performed (1.5 Tesla whole body magnetic resonance scanner). Six patients with acute leukemia were examined at diagnosis. Follow-up examinations of four patients with acute leukemia in complete remission were also examined. Six normal control subjects were examined with identical methods for comparison.
RESULTS
Significant differences could be detected in the spectral patterns from lumbar spine in patients with leukemia at diagnosis compared to healthy normal controls. The relative water content was increased in leukemic patients compared to normal subjects, which indicate an increase in the amount of hemopoietic tissue and a corresponding decrease in marrow fat content. A significant correlation was found between cellularity assessments derived from conventional bone marrow core biopsies and relative water content of proton MRS data. The Tl relaxation time of the water resonance in leukemic patients were significantly prolonged at diagnosis compared to normal controls. After chemotherapeutic induction of remission, the spectra from the bone marrow of lumbar spine resembled normal subjects.
CONCLUSIONS
This method provide the possibility for serial measurements of bone marrow in patients with leukemia, and may provide information from regions inaccessible to bone marrow biopsy. This therefore appears to be a promising application of proton MRS that can be performed on a routine basis in a clinical setting.

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Case Report

A Case of Invasive Aspergillosis Characterized by the Formation of Large Bronchial Cast in Patient with Acute Myelogenous Leukemia: Dong Woo Hyun, Dong Hwan Kim, Jin Tae Jung, Sang Kyun Sohn, Kyu Bo Lee; J Korean Cancer Assoc. 1998;30(5):1021-1025.

Abstract PDF: Invasive aspergillosis is a life-threatening infectious disease in immunocompromised patients. Prolonged neutropenia is the most important predisposing factor. Bronchial casts are generally associated with pneumonia, bronchiectasis, asthma, chronic bronchitis, allergic bronchopulmonary aspergillosis and mucoviscidosis. We experienced.a case of invasive aspergillosis characterized by the formation of large bronchial cast in patient with acute myelogenous leukemia(AML) during induction chemotherapy. The patient expectorated a large bronchial cast without airway obstruction. Aspergillus was disclosed in intraluminal surface of bronchial cast. The patient's conditions improved after amphotericin B therapy and expectoration of a large bronchial cast.

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Original Articles

Adenovirus - Mediated gene Transfer of Wild - Type p53 Results in Restoration of Tumor - Suppressor Function in Glioma Cell Lines: Mi Sook Kim, Hee Chung Kwon, Seok Il Hong, Choon Taek Lee, Seung Hoon Lee; J Korean Cancer Assoc. 1998;30(5):1026-1033.

Abstract PDF: PURPOSE
The replacement of functional genes into cells that lack genes or mutant genes is the basis of gene therapy. In cancer, where cells often have multiple genetic defects, the replacement of critical genes may suffice to suppress cell growth or induce cell death. In malignant brain tumors, p53 mutation are among the most frequently observed genetic findings and inactivation p53 suggests that p53 plays a critical role in carcinogenesis and tumor progression. Therefore, we study the successful transfer of the wild-type p53 gene using a replicative deficient adenovirus vector into human glioma and medulloblastoma c~ell lines. Meterials and Methods: The human glioma cell line T-98G, U-87MG, U-373MG were used. To determine the efficiency of the adenovirus vector, cell lines were transfected with the Ad-p gal and analysed with X-Gal staining. Cell viability was determined by trypan blue exclusion every day after infection and Westem blot analysis was used to conform the expression of the exogenous p53 protein.
RESULTS
Cell growth of the Ad-CMV-p53 infected U-373MG, and U-87MG was significantly suppressed. It appeared that exogenous p53 protein expression had an earlier ad more profound suppressive effect on U-373MG having a mutated p53 gene than on U-87MG having a wild-type p53. The expression of the exogenous p53 was more than 10 times higher than the expression of the endogenous p53. To examine the decreased viability, U-373MG was stained with Hochest 33258 and detected nuclear condensation and apoptic body. Staining results suggest that cells undergo apoptosis.
CONCLUSION
The replicative deficient adenoviral vector can transfer and express p53 in human glioma cell lines in vitro, restoring wild-type p53 tumor suppressor functions. The restoration of normal p53-encoded protein in the mutant ceil lines induced cell death. The high expression of the newly transduced protein had different effects on the growth rate of the infected cell lines depending on the p53 status of the cells.

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Effects of Herpes Simplex Virus - Thymidine Kinase Gene Transduction into the Hepatocellular Carcinoma Cell Lines Using the Retrovirus on Ganciclovir Cytoxicity: Joo Hang Kim, Jae Jin Song, Yoon Soo Chang, Eun Hee Kim, Jae Sung Kim, Heui Ran Lee, Jae Kyung Roh, Byung Soo Kim, Joong Bae Ahn, Nae Chun Yoo, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(5):1034-1043.

Abstract PDF: PURPOSE
Hepatocellular carcinoma (HCC) is one of the most common malignancy with high mortality in Korea. A new therapeutic modality such as gene therapy is necessary to improve the prognosis of hepatoma patients. Therefore we investigated the preclinical significance of Herpes simplex virus - thymidine kinase/ganciclovir (HSV-tk/GCV) gene therapy model using the retroviral vector for HCC cell lines.
MATERIALS AND METHODS
LNC/HSV-tk retroviral vector and PA317/LNC/HSV-tk pro- ducer cell line were constructed. HSV-tk transduced HCC cells using the LNC/HSV-tk retrovirus were selected by the G418 containing media. In vitro GCV sensitivity test of the HCC cells was performed by MTT assay. To evaluate in vivo GCV sensitivity, GCV was intraperitoneally injected after subcutaneous administration of HCC cells into each flank of the nude mouse.
RESULTS
HSV-tk gene transduction and expression in HCC cells were confirmed by RT-PCR. HSV-tk transduced HCC cell lines (SK-Hepl/HSV-tk and Hep-3B/HSV-tk) showed the marked GCV sensitivity comparing with the parental cell lines (SK-Hepl and Hep-3B) by MTT assay (p<0.001). The MTT test revealed that SK-Hepl/HSV-tk cells were more sensitive to GCV compare with that of Hep-3B/H5V-tk cells, and the parent cell line showed minimal growth suppression by the GCV treatment. In 12 nude mice received tumor cell mixtures of Hep-3B and Hep-3B/HSV-tk cells which contained more than 50% of HSV-tk transduced cells, the tumor was not developed in ll mice by the intraperitoneal administration of GCV. The tumors developed in 1 of 6 mice and 5 of 6 mice when mixtures contained 30% and 10% of HSV-tk transduced cells, respectively. Five mice out of 6 mice received inoculum containing the mixtures of 70% and 50% of HSV-tk transduced cells into each flank survived more than 6 month after HSV-tk/GCV treatment. Conelusion: HSV-tk gene transduced HCC cells showed the enhanced sensitivity to GCV. In nude mice HSV-tk/GCV strategy for HCC seemed to be more effective when tumor cell inoculum contained more than 30% of HSV-tk transduced HCC cells.

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p16INK4A and p15 INK4B Gene Alterations in Primary Uterine Cervical Carcinoma Tissues and Cervical Carcinoma Cell Lines: Sun Won Yoo, Jin Woo Kim; J Korean Cancer Assoc. 1998;30(5):1044-1052.

Abstract PDF: PURPOSE
Alterations of the p15(INK4B) and p16(INK4A) gene which are separated by 25 kb on chromosome 9p21 have been reported in various tumor derived cell lines and primary tumors, but the role of these genes in cervical cancer is unknown. MATERIAL AND METHOD: To determine the frequency of deletions and point mutations of these genes in human cervical cancer, we examined 57 primary tumors and matched normal tissues, and 3 cervical cancer derived cell lines. All the tumor tissues and cell lines were human papil- INK48 lomavirus (HPV)-positive. Deletions or point mutations of exon 2 of the pl5 gene and exons 1, 2, and 3 of the p16(INK4A) gene were examined by polymerase chain reaction (PCR) and direct sequencing, respectively.
RESULT
Our data indicate no evidence for intragenic homozygous deletion or point mutation in the cervical cancer or cervical cancer derived cell lines. INK48 INK4A CONCLUSION: Deletions or point mutations in the p15 or p16 gene may not be required for the development of HPV-positive cervical cancer or for establishment of cervical cancer cell lines.

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Concurrent Hyperfractionated Radiotherapy with CDDP / VP-16 Chemotherapy in Limited Stage Small Cell Lung Cancer: Hong Suck Song, Jin Hee Kim, Ok Bae Kim; J Korean Cancer Assoc. 1998;30(5):1053-1060.

Abstract PDF: PURPOSE
The aim of this study was to evaluate local control and long-term survival of concurrent hyperfractionated radiotherapy with CDDP/VP-16 chemotherapy in limited stage small cell lung cancer.
MATERIALS AND METHODS
From April 1992 to April 1997, twenty-nine patients with limited stage small cell lung cancer received cisplatin 25 mg/m plus etoposide 120 mg/m(2) on day 1, 2 and 3. Chemotherapy was repeated every 4 weeks for a total of 4 courses. Radiation was given to 60 Gy in 50 twice-daily fractionation separated by at least 6 hours, 5 days per week Thoracic radiotherapy was started with first coese of chemotherapy for 28.8 Gy. After 12 days break, radiotherapy was resumed with second course of chemotherapy for another 31,2 Gy.
RESULTS
Twenty-eight patients (96.6%) were evaluable. Patient characteristics include: median age 58.4 years (range 45-67); clinical stage 1IIa 13 pts, stage IIIb 15 pts; ECOG performance status 0 (8 pts), 1 (16 pts) and 2 (4 pts). Objective responses were 21 complete response, 6 partial response, 1 stable disease with overall response rate of 96.4%. Grade III and IV toxicities were leukopenia in 23/28 pts, thrombocytopenia in 8/28 pts, stomatitis in 10/28 pts, and alopecia in 8/28 pts. The median survival time was 19.2 months with 1 year, 2 year, 3 year, and 4 year actuarial survival rates and RFS are 65.6%, 30.6%, 30.6%, 24.5%, and 65.3%, 52.8%, 52.8%, 42.2%, respectively. Overall survival rate according to TNM stage, weight loss, age and sex were not statistically significant. Pattems of relapse were local only in 2 pts, systemic only in 7 pts, and local plus systemic in 1 pt, and brain was the most frequent systemic recurrent site (4 pts).
CONCLUSION
Concurrent hyperfractionated radiotherapy with CDDP/VP-16 chemotherapy seems to produce better local contml and survival rates in limited stage small cell lung cancer.

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