Cancer Research and Treatment

Germline Mutations of BRCA1 Gene in Korean Breast and/or Ovarian Cancer Families: Yong Jin Won, Jae Hwan Oh, Xiao Hong Huang, Dong Young Noh, Kuk Jin Choe, Soon Beom Kang, Lee Su Kim, Man Su Noh, Nam Sun Paik, Dae Hyun Yang, Se Min Oh, Soon Nam Lee, Jae Gahb Park; J Korean Cancer Assoc. 1997;29(5):713-723.

Abstract PDF: PURPOSE
To understand the involvement of BRCA1 gene in Korean breast and/or ovarian cancer families.
MATERIALS AND METHODS
Germline mutations of BRCA1 gene were analyzed in 13 families which included 3 hereditary site-specific breast cancer families, 6 suspected breast cancer families, and 3 suspected breast-ovarian cancer family, and one Li-Fraumeni family by screening BRCA1 gene using single strand conformation polymorphism (SSCP) analysis on polymerase chain reaction (PCR) amplified genomic DNA and confirmed the results by sequencing.
RESULTS
Including one family with previously reported nonsense mutation of BRCA1 gene, we detected two mutations in unrelated families. One newly identified mutation was frame shift mutation resulting from TG deletion in codon 1701, which results in a truncated BRCA1 protein, at codon 1714.
CONCLUSION
The proportion of families who inherit the mutated BRCA1 gene seems to be small among Korean breast and/or ovarian cancer families.

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Value of Phospholipase C gamma-1, Epidermal Growth Factor Receptor, and Her-2/neu in Human Breast Cancer: Ki Hoon Jung, Sung Han Bae, Eun Sook Lee, Jeoung Won Bae, Bum Whan Koo, In Sun Kim, Cheung Wung Whang; J Korean Cancer Assoc. 1997;29(5):724-737.

Abstract PDF: PURPOSE
Oncogen or growth factor receptor such as phospholipase C isoenzyme gamma-1 (PLC gamma-1), epidermal growth factor receptor (EGFR), and Her-2/neu which related with tyrosin kinasemay and then regulating vell proliferation may have a role as prognostic factors for breast cancer. MATERIAL AND METHODS: With assumption that expression of PLC gamma-1, EGFR and Her-2/neu oncogene has close relationship with prognosis of breast cancer, 59 breast cancer patients who were operated upon at Korea University Hospital during a period of 6 years starting June 1988 to May 1994 were selected for this study. This study was carried out by comparing between expression of PLC gamma-1, EGFR and Her-2/neu oncogene and patient's survival rate. These expression were also compared with TNM system, estrogen and progesterone receptor and at same time these expressions were compared with each other to see whether there are any relationship among these expression.
RESULTS
Expression of PLC gamma-1, EGFR and Her-2/neu were present in 42% (25/59), 46% (27/59) and 20% (12/59). The expression of PLC gamma-1 was closely related with the expression of EGFR (p<0.05) and Her-2/neu (p<0.05), but there were no relationship between the expression of PLC gamma-1 and hormonal receptors and TNM stage (p>0.05). The expression of EGFR was closely related with the expression of Her-2/neu (p<0.05) and hormone receptors (p<0.05), but there were no relationship between the expression of EGFR and pathologic TNM stage (p>0.05). The expression of Her-2/neu was not closely related with hormone receptors and TNM stage except axillary lymph node metastasis. There were close relationship between overall and disease free survival and PLC gamma-1 and Her-2/neu. But EGFR had only related with disease free survival rate.
CONCLUSION
In conclusion, the expression of PLC gamma-1, EGFR and Her-2/neu oncogene in human breast cancer may be useful prognostic factors independently and it may potentiated its individual value as a prognostic factors if use them together.

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The Significance of DNA Flow-cytometry in Breast Cancer: Ja Yun Koo, Hy De Lee, Woo Hee Jung; J Korean Cancer Assoc. 1997;29(5):738-747.

Abstract PDF: PURPOSE
To evaluate the relationship between nuclear DNA contents and prognostic factors and survival in breast cancer patients.
MATERIALS AND METHODS
We determined nuclear DNA content from 91 paraffin-embedded malignant breast tumors and evaluated relationship between DNA nuclear content and well-known prognostic indicators of breast cancer and the survival of the patients by statistical analyses.
RESULTS
Twenty nine (34.5%) of the 91 tumors examined were diploid, and the remainder (65.5%) contained one or more aneuploid clones. S-phase fraction (SPF) ranged from 1.4 to 68.3% (median 11.2%) and it was higher in aneuploidy tumors than in diploid tumors (p<0.05). Positive axillary lymph nodes were found in 72.7% of the patients who had a tumor with a high SPF (above the median 11.2%) and in 27.3% of those with tumor with low SPF (below median) (p<0.05). The overall survival rate was 96.1% in DNA diploid and 87.6% in DNA aneuploid tumors, showing that DNA ploidy had no prognostic significance in breast cancers. The actuarial survival rates were 96.4% and 86.3% for low and high SPF, respectively (p=0.28). The patients with high SPF showed high disease free survival rate compared to the patients with low SPF but the difference had no statistical significance.
CONCLUSION
Our results indicate DNA aneuploid tumors were more prevalent in breast cancer patients with high SPF or lymph node metastasis and larger patient accumulation with longer follow-up period will be helpful to identifiy the relationship between flow- cytometrical analysis and prognosis.

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Reclassification of the Medullary Carcinoma and It's Clinical Characteristics: Sang Kyu Kim, Chang Yong Sohn, Koo Jeong Kang, You Sah Kim, Eun Sook Chang; J Korean Cancer Assoc. 1997;29(5):748-753.

Abstract PDF: PURPOSE
Reclassfication of the medullary carcinoma using a strict histologic criteria and analysis of the clinical and pathological characteristics of the medullary carcinoma. MATERIAL & METHODS: Thirty-seven cases of the breast carcinoma originally diagnosed as medullary carcinoma were reviewed. One to ten microscopic slides of each case were reexamined and reclassified using the strictly defined histologic criteria defined by Ridolfi et al. Tumors were excluded from the category of the typical medullary carcinoma (TMC) on the basis of presence of glandular features, focal marginal infiltrations, or sparse mononuclear infiltrations. Tumor with two or more atypical features, or extensive marginal infiltrations, no mononuclear cell infiltration and/or less than 75% syncytial growth were classified as infiltrating ductal carcinoma with medullary feature (IDC). A predominantly syncytial growth pattern (75% or more) was requisite for inclusion in both TMC and atypical medullary carcinomas (AMC).
RESULTS
Twenty-two tumors (60%) fulfilled the criteria for TMC, and 12 tumors (32%) were AMC and three tumors (8%) were IDC. TMC occupied 3.1% of breast cancer. The mean age of patients with TMC was 45.4+/-11.2 years and the average size of the tumor in TMC was slightly larger than that of breast cancer in general, although not statistically significant. The frequency of lymph node metastasis in TMC was similar to breast cancer in general. Five year survival of patients with TMC was 95.5% which was significantly better than breast cancer in general.
CONCLUSION
The TMC occupied 3.1% of breast cancer. The mean age of patient, tumor size and lymphnode metastasis were not different from that of breast cancer but 5 years survival of patient with TMC was significantly better than breast cancer in general.

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A Study of Retrovirus-mediated p53 Gene Transduction Into Human Gastric Cancer Cell Lines: Joo Hang Kim, Yoo Sun Moon, Dong Hwan Shin, Jae Jin Song, Soo Jung Gong, Sun Young Rha, Soo Kyoung Kim, Sook Jung Jeong, Hyun Cheol Chung, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(5):754-764.

Abstract PDF: PURPOSE
The development of new therapeutic modalities such as gene therapy, which still requires further investigation, is clearly important to improve the prognosis of gastric cancer. This study was conducted to evaluate the effect on the growth and the tumorigenicity of retrovirus-mediated p53 gene transduction into gastric cancer cells.
MATERIALS AND METHODS
Human gastric cancer cell lines were cultured and their DNAs were analyzed to evaluate the p53 status with PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) and DNA sequencing. Retroviral supernatants were obtained from each producer cell line, PA317/LNCX and PA317/LNC/p53, after construction of retroviral vector LNC/p53 containing human p53 cDNA and producer cell line PA 317/ LNC/p53. To investigate the effect of retrovirus-mediated p53 gene transduction in human gastric cancer cell lines, the in vitro growth rates and in vivo tumorigenicities of the N-87 cell line having mutant p53 and the YCC-S-2 cell line having wild-type p53 were compared before and after infection with LNC/p53 retrovirus. RESULTS: The following results were obtained: 1) The growth inhibition of N-87 cells after p53 transduction was signficant when compared to that of the parent N-87 cells. The growth of the p53 transduced YCC-S-2 cells and the parent YCC-S-2 cells was not different. 2) In nude mice, the growth of tumors formed by N-87 cells was modestly inhibited after retrovirus-mediated wild-type p53 gene transduction. However, the growth of tumors formed by YCC-S-2 cells was not inhibited by retrovirus-mediated p53 gene transduction. 3) The expression rate of p53 protein after p53-containing retroviral infection in the KATO-III cell lines, which have no p53 gene, was dose-dependent on the m.o.i. of retrovirus, although it was not more than 15% with the m.o.i. of 100 upon immunohistochemical analysis.
CONCLUSION
The growth inhibition by retrovirus-mediated p53 transduction in human gastric cancer cells was significant in a gastric cancer cell line having mutant p53 in vitro, and the growth of tumor masses formed by a gastric cancer cell line having mutant p53 was modestly inhibited after p53 transduction using retroviral vector in nude mice, although it was not statistically significant. Only modest inhibition of tumor growth using retrovirus-mediated p53 gene transduction in vivo is most likely to be due to low transduction efficiency.

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Clinical Significance of Urokinase-type Plasminogen Activator (uPA) Expression from Serum and Tissue of Gastric Cancer Patients: Hyun Cheol Chung, Joon Oh Park, Hyun Ja Kwon, Tae Soo Kim, Hei Cheol Chung, Soo Jung Gong, Hwa Young Lee, Sun Young Rha, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Sung Hoon Noh, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(5):765-773.

Abstract PDF: PURPOSE
We measured the gastric cancer tissue uPA and plasminogen activator inhibitor-1 (PAI-1) levels and compared them to those of the peripheral and portal blood levels to evaluate the correlation.
MATERIALS AND METHODS
Tissue uPA and PAI-1 levels were measured by ELISA assay (Monozyme, Netherland) in paired 85 normal and cancer tissues resected from gastric cancer patients. In 50 patients, blood uPA and PAI-1 levels were measured from pre- operative peripheral and portal blood, post-operative portal blood.
RESULTS
Gastric cancer tissue uPA and PAI-1 levels increased from the early stage. The elevated cancer-to-normal ratios of the uPA and PAI-1 were constant from stage I to IV. There were correlations of uPA between normal and cancer tissues (r2=0.38) and between peripheral and pre-resection portal blood level (r2=0.64). There were no correlations between tissue PAI-1 level and blood PAI-1 levels. However, there were correlations in PAI- 1/uPA ratio between cancer tissue and peripheral blood (r2=0.25), peripheral blood and pre- resection portal blood (r2=0.60).
CONCLUSION
Even if the cancer tissue levels of uPA and PAI-1 increased from the early stage of gastric cancer, only blood uPA level correlated with tissue uPA level. A modest correlation found in PAI-1/uPA ratio between cancer tissue and blood suggests applicability of blood PAI-1/uPA ratio in predicting tissue uPA, PAI-1 expression.

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The Expression of c-myc and AAT in Gastric Carcinoma: Sun Mi Park, Ho Dae You, Pok Keun Kim, Won Sup Oho, Seon Ja Park, Man Ha Huh, Ja Young Koo; J Korean Cancer Assoc. 1997;29(5):774-784.

Abstract PDF: PURPOSE
We have conducted this study to investigate the role of c-myc and AAT in gastric carcinoma progression and to see if clinical application of its expression in cancer tissue is of help for the diagnosis or in determining prognosis of gastric carcinoma.
MATERIALS AND METHOD
The expression of c-Myc and AAT by immunohistochemical method applied to paraffin-embedded tissue sections of endoscopic biopsy materials of 71 cases of gastric carcinoma (24 early and 47 advanced) and immunoreactivities of antigens were correlated with histological differentiation of carcinoma, degree of tumor infiltration of mononuclear cells, serum levels of carcinoembryonic antigen (CEA) and presence of distant metastases.
RESULTS
c-Myc in gastric carcinoma tissue was expressed in 24 cases (33.8%), and the rate of immunoreactivity of c-Myc was higher in the advanced carcinoma cases (38.2%) than early carcinoma cases (25.0%), but the difference was not stastistically significant. The elevated c-Myc expression correlated well with the elevation of serum CEA levels (P<0.05), with the presence of distant metastses (p<0.05), especially with peritoneal metastsis (p<0.05). AAT expression in gastric carcinoma was shown in 11 cases (14.1%), and the rate of immunoreactivity of AAT was significantly higher in advanced carcinoma cases (21.3%) than early carcinoma cases (4.2%) (p<0.05). The elevated expression of AAT correlated well with the elevation of serum CEA levels (p<0.05), and showed negative correlation with the degree of mononuclear cell infiltration in tumor area (p<0.05). The increased expression of c-Myc and AAT in gastric carcinoma correlated well (p=0.05, k= 0.31), which suggests the cooperative action of the two in gastric carcinoma progression.
CONCLUSIONS
Our findings suggest that c-Myc expression may be a good marker of high grade malignancy in gastric carcinoma, and may be able to be used clinically in predicting distant metastases, especially for peritoneal dissemination. Our data also imply that c-myc, through its proliferative action, may play an important role in the progression of gastric carcinoma in cooperation with AAT which has immunosuppresive action.

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Effects of Lovastatin in Combination with 5-FU on Stomach Cancer Cells: Chaehwa Park, Won Ki Kang; J Korean Cancer Assoc. 1997;29(5):785-790.

Abstract PDF: No abstract available

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Post-operative Adjuvant Chemotherapy with 5-Fluorouracil, Leucovorin, and Mitomycin C (MLF) for Gastric Cancer: Jong Ho Chun, Dong Kyu Kim, Moon Suk Jo, Hyeong Jun Kim, Jung Il Won, Sung Rok Kim, Hong Yong Kim; J Korean Cancer Assoc. 1997;29(5):791-799.

Abstract PDF: PURPOSE
The surgical resection has been still the only curative treatment modality for the gastric cancer, but the overall prognosis has not been so satisfactory because of high relapse rate. So the necessity of adjuvant chemotherapy has been increased. We evaluated the effect of MLF (5-fluorouracil, leucovorin and mitomycin C) regimen on the prevention of relapse and survival benefit after postopertive adjuvant chemotherapy.
MATERIALS AND METHOD
The MLF regimen consisted of 5-FU 375 mg/m2 IV on days 1 through 5; LV 20 mg/m2 IV just before 5-FU infusion on days 1 through 5; and MMC 9 mg/m2 IV on day 1 (7 mg/m2 from the 2nd cycle).
RESULTS
One hundred patients were entered into the trial; 56 were male & 44 female, and the range of age was 20 to 82. The total number of chemotherapy cycles was 514. According to AJCC staging, 4 cases were in stage IA, 14 IB, 23 II, 42 IIIA, 15 IIIB, respectively and 2 cases were in stage IV. The estimated median survival was 32 months in stage IIIA, and 28 months in IIIB. The 5 year survival was 90% in stage IB, 76% in II, 29.6% in IIIA and 21.8% in IIIB. Severe neutropenia (WHO grade > or = 3) was observed in 11.8%, and throbocytopenia 0.4%. Severe nausea and vomiting was observed in 1.8%, diarrhea in 1.7%, and mucositis in 1.5%, but there was no toxic death.
CONCLUSION
The MLF adjuvant chemotherapy may be effective for resectable gastric cancer with minimal toxicities, but phase III study is needed to confirm its efficacy.

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The Effects of Mesima-Ex, the Immunomodulator in Curatively Resected Gastric Cancer: Se Haeng Cho, Joo Hang Kim, Byung Kyu Park, Soo Jin Park, Sang Hun Ahn, Hyun Chul Jung, Jae Kyung Rho, Byung Soo Kim, Sung Hun Rho; J Korean Cancer Assoc. 1997;29(5):800-806.

Abstract PDF: PURPOSE
The Mesima-Ex is a kind of biologic response modifier, which is extracted from a mushroom called Phellinus linteus. Mesima-Ex consists of various chemical compounds which include protein bound polysaccharide, mucoprotein, triterpenoid, and quinones. Mesima-Ex exerts its antitumor effects by augmenting host immune response without any toxic side effects. In vitro study, Mesima-Ex seems to potentiates antibody dependent cell mediated cytotoxicity (ADCC) and cell mediated cytotoxicity (CMI) against tumor cells. We initiated this study to verify antitumor effects of Mesima-Ex as an antineoplastic agent.
MATERIALS AND METHOD
Gastric cancer patients who underwent curative resection with normal hepatic and renal function were eligible. They were divided into two groups by random number table. One group (N=30: Mesima-Ex group) received postoperative adjuvant chemotherapy with 5-FU (500 mg/m2 weekly), adriamycin (40 mg/m2 every 3 weeks) and Mesima-Ex (6 cap daily per Os). Another group (N=37: control group) received 5-FU and adriamycin only without Mesima-Ex. NK (natural killer cell) activity, ADCC (antibody dependent cell mediated cytotoxicity), CD4 , and CD8 cells were measured and an analysis of disease free survival rate of the two study groups was performed.
RESULTS
Sixty seven patients were enrolled in this study. Their median age was 55 years old. NK activity (basal activity: 25%) was enhanced significantly at the 2nd, and 4th months in the Mesima-Ex group (28.9%, 43.4%, p<0.05). ADCC was also enhanced from 37% to 42.1% at the 2nd month in the Mesima-Ex group (p<0.05). The control group did not show any significant change in NK activity or ADCC. The CD4 cell ratio was increased from 37% to 42.1% at the 2nd months in the Mesima-Ex group but not in the control group (p<0.05). There was no significant change in CD8 subsets (p>0.05). There were no toxic side effects more than grade III from Mesima-Ex administration. The two year disease free survival rate was higher in the Mesima-Ex group than that of the control group (77% vs 58%, p<0.05).
CONCLUSION
Mesima-Ex can be used safely as an immunomodulator with standard chemotherapeutic agents for purpose of adjuvant chemotherapy. Mesima-Ex was effective in augmenting host immune response in vitro. The Mesima-Ex group showed a higher two year disease free survival rate than that of the control group.

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The Effect of Neoadjuvant Chemotherapy with 5-Fluorouracil (5-FU), Vinblastine and Cisplatin (FVP) for Stage III Non-Small Cell Lung Cancer (NSCLC): Jung Il Won, Jong Ho Chun, Hyeong Jun Kim, Moon Suk Jo, Dong Kyu Kim, Young Tae Kwak, Jung Suk Kim, Soo Jeon Choi, Sung Rok Kim; J Korean Cancer Assoc. 1997;29(5):807-815.

Abstract PDF: PURPOSE
As the prognosis of stage III NSCLC is still poor with or without operation, we conducted a phase II trial of neoadjuvant chemotherapy (CHT) with 5-FU, vinblastine, cisplatin prior to surgery to determine the effect on resectability and survival.
MATERIALS AND METHOD
Patients (pt) received 5-FU 500mg/m2/12 hours continuous infusion for 36 hours, vinblastine 3mg/m2/day iv bolus day 1 and day 2, and cisplatin 75mg/m2 iv day 1 every 3 weeks. This regimen was given for 2 cycles. When the tumor was responsive (stable disease or better), 1 or 2 more cycles of the CHT were given, followed by operation when totally resectable on chest CT/MRI, then 3 more cycles of the CHT to finish the treatment; when the tumor was neither responsive nor resectable after 3rd or 4th CHT, radiotherapy was started.
RESULT
Twenty nine pt were enrolled and 26 pt have been evaluable so far. Age ranged from 32 to 79 (median 59 years); 23 were male, 3 female. Total of 108 cycles were given (mean 4.2). There were 4 partial remissions out of 6 IIIAs (67%) and 10 out of 20 IIIBs (50%), with overall response rate of 53.8%; down staging was noted in 9 patients (34.6%). 9 pt (34.6%) underwent curative resection successfully; 4 out of 6 IIIAs (67%) and 5 out of 20 IIIBs (25.0%); 1 patient refused operation. Median survival was 31.3 months for 9 pt with operation, and that of all patients was 14.2 months. Radiation was given to 9 pt, resulting in 3 partial remissions (PR), 3 stable diseases (SD), 3 progressive diseases (PD). Serious (WHO grade> or =3) toxicities were nausea/emesis in 2.8%, granulocytopenia in 26.9% and thrombocytopenia in 2.8%.
CONCLUSION
This treatment modality seemed to be effective, encouraging further phase III study for better determination of its role.

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Evaulation of Angiogenesis and Matrix Metalloproteinase as Prognostic Markers in Squamous Cell Carcinoma of the Lung: Young Sik Kim, Young Bae Kim, Dong Hwan Shin, Han Kyeom Kim, Bum Woo Yeom, Jong Sang Choi, Insun Kim, Dale Lee; J Korean Cancer Assoc. 1997;29(5):816-824.

Abstract PDF: PURPOSE
In squamous cell carcinomas of the lung, the angiogenesis and the expression rates of metalloproteinase were measured to examine whether they can be useful as prognostic markers and therapeutic potentials.
MATERIALS AND METHODS
The angiogenesis and the expression rates of metalloproteinase were analyzed by counting the number of microvessels and immunohistochemically positive cells of MMP-1 and MMP-2 in 54 squamous cell carcinoma, respectively.
RESULTS
Lymph node meatastasis group showed higher angiogenesis than non-metastasis one (p=0.008). Angiogenesis were elevated with increasing clinical stage. However, MMP-1 and MMP-2 expression rate as the presence or absence of lymph node metastasis and the clinical stages were statistically insignificant, respectively. Angiogenesis failed to demonstrate any significant correlation with the expression rates of MMPs.
CONCLUSION
Our results suggests that angiogenesis level may provide informaton relevant to prognosis as well as treatment decisions.

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Age-related Clinical Characteristics and Outcome of Hepatic Resection Therapy in Hepatocellular Carcinoma Patients: Ok Ku Cho, Dong Sup Yoon, Sung Won Kwon, Hoon Sang Chi, Byung Ro Kim; J Korean Cancer Assoc. 1997;29(5):825-831.

Abstract PDF: PURPOSE
A retrospective clinical study of 213 patients who underwent curative resection due to hepatocellular carcinoma was performed in order to compare the mortality and survival rates of elderly patients with those of younger patients following the resection.
MATERIALS AND METHODS
All subjects underwent curative resection at Shinchon & Yongdong Severance Hospital between January 1985 to December 1994. The subjects were classified into three age groups: Group I (n=26) under 40, Group II (n=142) between 41 and 60, and Group III (n=45) over 60. Variables considered include sex, family history, accompanied diseases, Hbs Ag, -PF, Child classification, operative method, resection margin, number of mass, size of mass and gross-appearance were evaluated by X2-test (p=0.05). The one, three and five year survival rates were analysed in each group by the Kaplan- Meyer method and survival curves were compared by the log-rank test. A probability of <0.05 was accepted as significant.
RESULTS
The results showed that elderly patients have no significant differences from the younger patients in any of the variables considered including postoperative morbidity, survival rate and disease-free survival rate, except for the family history and positive Hbs Ag in which the elderly patients showed significantly lower values.
CONCLUSION
These results suggest that hepatocellular carcinoma in the aged can be treated in identical manner as in younger patients.

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The Results of Radiation Therapy in Patients with Cancer of the Esophagus: Jun Sang Kim, Moon June Cho, Jae Sung Kim, Hyun Yong Jeong, Young Lee; J Korean Cancer Assoc. 1997;29(5):832-841.

Abstract PDF: No abstract available

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Evaluation of Staging with MR Imaging in the Uterine Cervical Cancer: Woo Cheol Kim, Hae Jeong Jeon, Soon Gu Cho, Young Kap Cho, John K Loh; J Korean Cancer Assoc. 1997;29(5):842-850.

Abstract PDF: PURPOSE
Uterine cervical carcinoma is the most common cancer in Korean women. We evaluated the accuracy of magnetic resonance (MR) imaging in determining the stage and extent of disease in cervical carcinoma.
MATERIALS AND METHODS
From January 1994 through December 1996, in all 35 patients, MR imaging was performed before any operative procedure. With a 1.5T superconducting magnet, TR (repetition time)/TE (echo time) of 483/9msec for T1-weighted images and 3750/98msec for T2-weighted images were used. All patients underwent radical hysterectomy or total abdominal hysterectomy and had detailed histologic evaluation. MR image were reviewed and compared with pathologic findings on the presence of tumor size, depth of stromal invasion and vagina extension.
RESULTS
The accuracy of MRI in determination of stage was 74%. Its accuracy was 60% for the assessment of tumor size. Tumor size was underestimated in 6 patients (17%) and overestimated in 8 patients (23%). Tumor infiltration into the stroma was classified as no, partial, complete. The accuracy of MRI in cervical stromal invasion was 66%.
CONCLUSION
MR is a relatively promising method for staging and evaluating extent of disease in carcinoma of the uterine cervix.

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Significance of Epstein-Barr Virus Detection in non-Hodgkin's Lymphoma in Korea: Chang In Suh, Bum Joon Kim, Jae Won Park, Eung Soo Hwang, Yoon Hoh Kook, Chang Yong Cha; J Korean Cancer Assoc. 1997;29(5):851-866.

Abstract PDF: PURPOSE
To investigate whether non-Hodgkin's lymphoma of Korea is pathogenetically associated with Epstein-Barr virus (EBV).
MATERIALS AND METHODS
We analyzed fifty nine paraffin-embedded tissue and 22 fresh frozen tissue samples from non-Hodgkin's lymphoma patients for the presence of EBV sequences by polymerase chain reactions (PCR), in situ hybridization (ISH) and assessed the clonality of EBV infected cells by Southern blot hybridization.
RESULT
On ISH using oligonucleotide probes corresponding to EBV-encoded small RNAs (EBERs), 17 (28.8%) of 59 paraffin-embedded tissue samples showed positive hybridization signals localized over the nuclei of the tumor cells, but PCR using primers from Internal Repeat I or EBV-determined nuclear antigen 1 gene showed positive results in only 6 (10.2%) and 5 (8.5%) samples, respectively. ISH and PCR did not detect EBV sequences in 15 paraffin-embedded tissue samples of tuberculous lymphadenitis patients. In 22 fresh frozen tissue samples, PCR detected EBV sequences in three samples from peripheral T cell lymphoma (PTCL). In two of those three samples, Southern blot analysis showed that these viral DNAs were monoclonal and of latent form.
CONCLUSION
Approximately 28.8% of non-Hodgkin's lymphoma were related to EBV in Korea. Monoclonality of those EBV DNAs implies that virus infection preceded malignant transformation, suggesting that EBV may play a role in lymphomagenesis.

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Immunohistochemical Study on Expression of the p53 Protein in Medulloblastoma/PNET: Eun Jung Kim, Sang Soo Park, Young Ho Lee, Ahn Hong Choi, Seo Hee Rha, Soon Yong Lee, Hye Kyoung Yoon, Young Tak Lim, Do Yoon Park, Kang Suek Suh; J Korean Cancer Assoc. 1997;29(5):867-873.

Abstract PDF: PURPOSE
The present study explores the expression rate of p53 mutation and the correlation between the expression of p53 protein and prognostic factors in medulloblastoma/ PNET (primitive neuroectodermal tumor).
MATERIALS AND METHODS
We studied retrospectively 24 patients with medulloblastoma/ PNET, who were admitted in Dong-A University Hospital, Pusan National University Hospital and Inje University Pusan Paik Hospital from 1988 to 1995. Detection of p53 mutations was made by immunohistochemical staining of p53 protein on paraffin- embedded tissues. The correlation between the expression of p53 protein and prognostic factors was evaluated by the Spearman correlation analysis.
RESULTS
p53 protein was expressed in 6 of 24 patients (25%). In 20 patients who could be evaluated for metastasis, 16 patients of M0, 1 patient of M1 and 3 patients of M2 were grouped by M stage, and the expression of p53 was detected in 1 of 16 M0 group (6.3%) and 3 of 3 M2 group (100%). p53 expression was significantly related to the M stage of medulloblastoma/PNET (r=0.73, p<0.001). The detection of p53 was not significantly associated with T stage, cellular differentiation and the relapse rate of medulloblastoma/ PNET.
CONCLUSION
The immunohistochemical detection rate of p53 protein in medulloblastoma/ PNET was 25%. The expression of p53 protein was significantly related to the M stage, with higher expression rate in M2 group of medulloblsatoma/PNET.

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A Preliminary Report of Busulfan, Melphalan and Thiotepa or TBI-containing Bi-alkylator Chemotherapy as a Preparative Regimen for Allogeneic Bone Marrow Transplantation in Refractory or Relapsed Acute Leukemias: Hee Je Kim, Woo Sung Min, Sung Kyu Park, Dong Wook Kim, Jong Wook Lee, Chi Hwa Han, Chun Choo Kim, Dong Jip Kim; J Korean Cancer Assoc. 1997;29(5):874-885.

Abstract PDF: PURPOSE
We assessed the three-alkylator combination of busulfan, melphalan and thiotepa or TBI, melphalan and thiotepa conditioning for allogeneic stem cell transplantation in 7 adult patients with refractory or relapsed acute leukemias.
MATERIALS AND METHODS
Six patients were transplanted for acute myeloid leukemia, one for acute lymphoblastic leukemia and included 5 of relapsed refractory, 2 of relapsed after first-BMT. All but 1 cases received G-CSF stimulated CD34+ allogeneic peripheral blood progenitor cells (PBPCs) in addition to stimulated allogeneic marrow.
RESULTS
All patients except one engrafted (median time to ANC >0.5 10 (9)/L=11days, to platelets >30 X 10 (9)/L=14 days) successfully and complete remission was obtained in 6 patients. Grade I-II acute GVHD and controllable regimen-related toxicity especially oral mucositis (grade II-III) developed in all cases, but 2 patients including one second- allogeneic BMT patient expired early by transplant-related toxicity of hepatic or multiorgan failure along the course of sepsis.
CONCLUSION
Although the observation period on these cases are limited, the data presented show that the combination of busulfan, melphalan and thiotepa is tolerable as a preparative regimen for allogeneic marrow transplantation in high-risk leukemic patients. We think that these encouraging results need to be confirmed in prospective studies in the future.

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A Phase I/II Trial of DA3030 in Chemotherapy Induced Neutropenia: Hyun Cheol Chung, Sun Young Rha, Soo Jung Gong, Hwa Young Lee, Hei Cheol Chung, Churl Woo Ahn, Wook Jin Chung, Rutha Lee, Bo Young Choung, Seung Keun Lee, Yoon Soo Chang, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Bum Soo Park, Mi Young Bahng; J Korean Cancer Assoc. 1997;29(5):886-898.

Abstract PDF: PURPOSE
We planned to evaluate the toxicity and efficacy of DA-3030 to determine the recommended dose for phase III clinical trial based on the biologically active doses from phase I/II clinical trial.
MATERIALS AND METHODS
Open non-randomized phase I/II study was carried out in 64 cancer patients with chemotheray-induced myelosuppression. After 1 cycle of control period (chemotherapy without DA-3030), DA-3030 was started 24 hours after the second cycle of chemotherapy to 4 groups of patients with the doses of 50 microgram/m2/day (step I), 100 microgram/m2/day (step II), 150 microgram/m2/day (step III), 200microgram/m2/day (step IV) by once-a-day subcutaneous administration for 10 days.
RESULTS
Of the 64 enrolled patients, 46 patients were evaluable. Tmax reached after 2 hours of injection in step I and 4 hours in step II-IV. Terminal half life was 1.8 hours in step I and 3.2 hours in step II, 3.3 hours in step III, 3.0 hours in step IV. Area under the curve (AUC) and AUMC increased dose dependently from step I through step IV. Total clearance rate decreased in a dose dependent manner but the volume of distribution showed no differences between the steps.The mean nadir count of total WBC and neutrophil increased in all 4 steps of DA-3030 administration. Also the duration of leukopenia, equal to or less than 2,000/uL or neutropenia and the recovery time of WBC or neutrophil from nadir decreased with DA-3030 administration in all 4 steps. But no differece of DA-3030 effect was found among 4 steps. When we compared the clinical efficacy of DA-3030 with total WBC and neutrophil criteria, it was 58.3% and 58.3% in step I, 90.0% and 80.0% in step II, 91.7% and 91.7% in step III, 75.0% and 70.0% in step IV. Although the duration of antibiotics administration showed no difference between control and DA-3030 administration period in step I, it decreased with DA-3030 administration in step II-IV. Infection was found only in step I. Life-threatening side effect was not found in all steps. Only mild myalgia was found without any dose relationship.
CONCLUSION
When we considered the efficacy, toxicity and pharmacokinetic parameters, we suggest that 100microgram/m2 is an appropriate dosage for the phase III clinical trial.

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A Clinical Analysis of Primary Small Bowel Cancer: Ki Sun Kil, Jin Sun Bae; J Korean Cancer Assoc. 1997;29(5):899-905.

Abstract PDF: PURPOSE
Primary small bowel cancer is rare. In many cases, the diagnosis is difficult especially in jejunum and ileum, confirmed in advanced state with poor prognosis. This study was intended to clarify the characteristics of primary small bowel cancer. MATERIAL AND METHOD: We have reviewed 24 patients with primary small bowel cancer that have been operated at the Department of Surgery, hospital from Jan. 1990 until Dec. 1996. The clinical feature, diagnostic method, location and histologic finding of tumor, prognosis were analyzed.
RESULTS
1. The ratio of male to female was 1:1.18. The mean age was 53 years and the most prevalent age group was 6th decade (13 cases, 54.1%). 2. The most common primary site was jejunum (9 cases), followed by duodenum (8 cases) and ileum (7 cases). Leiomyosarcoma occurred most frequently in jejunum, adenocarcinoma in duodenum, and lymphoma in ileum. 3. The most common symptom was abdominal pain (66.7%), followed by anemia (54.2%), palpable mass (50%). 4. The accuracy rate of preoperative diagnosis or suspicion was 45.8%, and diagnostic measures were endoscopy in duodenum, small bowel series and/or abdominal CT. in jejunum and ileum. 5. Curative resection was performed in 14 cases (58.3%), and the cancer in which palliative resection was undertaken most frequently was leiomyosarcoma. 6. The mean follow-up period of 23 cases except 1 was 33 months, during this time 9 cases were dead, of whom 5 cases had leiomyosarcoma.
CONCLUSION
Frequently, small bowel cancer is difficult in diagnosis, confirmed in late stage. High degree of suspicion and more endeavor to discover it is important and needed to bring a better result.

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Four Cases of Typhlitis, Developed in Neutropenic State and Treated with Medical Conservative Management: Pill Woon Kim, Hyeon Gyoo Ji, Hyun Sik Jeong, Chan Il Moon, Dong Kyeong Yang, Seung Won Lee, Yon Sil Jung, Ji Ho Choi, Gui Hyun Nam, Jae Hoon Lee, Dong Bok Shin; J Korean Cancer Assoc. 1997;29(5):906-913.

Abstract PDF: Typhlitis is a life threatening necrotizing enterocolitis of the cecum, ascending colon and terminal ileum seen in severely neutropenic patients, however its pathogenesis is not identified up to this time.The incidence of typhlitis in leukemic patient is 10~12%, estimated by postmortem examination, and 46% in induction chemotherapy of leukemia. Recently, entity incidence is more high due to increasing challenges to high dose chemotherapy in solid tumors.We experienced four cases of typhlitis, one was developed in the circumstance of neutropenia induced by induction chemotherapy for acute myelocytic leukemia and others in neutropnia due to primary diseases without chemotherapy, ig, chronic myelocytic leukemia, acute lymphocytic leukemia, myelodysplastic syndrome.All cases were treated with high dose broad spectrum antibiotics in early phase of disease and its outcome was good, so that, early diagnosis of typhlitis is essential, then prompt treatment with high dose antibiotics and intravenous fluid before onset of transmural necrosis is associated with lower morbidity and mortality than surgical resection.

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A Report of Hepatocellular Carcinoma with Renal Metastasis: Seung Hyuk Choi, Seung Won Choi, Young Nyun Park, Ho Guun Na, Sun Young Rha, Hyun Cheol Chung, Joo Hang Kim, Jae Kyung Roh, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(5):914-914.

Abstract PDF: Hepatocellular carcinoma is a fatal disease with median survival less than 6 months. About 50% of hepatocellular carcinoma patients showed distant metastasis at earlier stage. Common metastatic sites are lung, intraabdominal lymph nodes, adrenal gland or bone, in order of frequency. Renal metastasis from hepatocellular carcinoma is rare with the incidence of 1.2-4.3% at autopsy. Lack of clinical symptoms and signs make it difficult to diagnose metastatic renal cancer before dying of. Common primary sites of metastatic renal cancer are malignant lymphoma, lung, stomach or breast. We report a case of hepatocellular carcinoma with renal metastasis. A 54 female patient was found to have coincidental right hepatic and right renal tumors on abdominal ultrasonographic and computed tomographic examinations. After the percutaneous needle biopsy on the right hepatic tumor and right renal tumor, histopathologic and immunohistochemical studies ultimately confirmed the diagnosis of hepatocellular cracinoma with renal metastasis. Intraarterial chemotherapy with cisplatin for primary hepatocellular carcinoma and intraarterial embolization for renal metastatic lesion were performed.

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