Jun Eun Park, O Kyu Noh, Yonghee Lee, Hyoung Soo Choi, Jung Woo Han, Seung Min Hahn, Chuhl Joo Lyu, Ji Won Lee, Keon Hee Yoo, Hong Hoe Koo, Seon-Yong Jeong, Ki Woong Sung
Cancer Res Treat. 2020;52(2):438-445. Published online September 10, 2019
Purpose Loss of heterozygosity (LOH) at chromosomes 1p and 16q is a poor prognostic factor in favorable histology Wilms tumor (FHWT). This study investigated the prevalence of LOH at 1p and 16q and evaluated its prognostic value in Korean children with FHWT. Materials and Methods We analyzed 101 FHWT patients who were diagnosed between 1996 and 2016 in Korean Society of Pediatric Hematology Oncology Group hospitals. Using paraffin-embedded kidney tissue samples sent from each center, we reviewed LOH at 1p and 16q in each patient and assessed the prognostic value of LOH status for clinical parameters affecting event-free survival (EFS).
Results Of the 101 patients, 12 (11.9%) experienced recurrence; the 3-year EFS was 87.6%. LOH at 1p or 16q was detected in 19 patients (18.8%), with five having LOH at both 1q and 16q. The frequency of LOH at 1p was higher among younger patients (p=0.049), but there was no difference in LOH prevalence according to tumor stage. In the multivariate analysis, LOH at 16q was a significant negative prognostic factor affecting EFS (3-year EFS, 73.7% vs. 91.1%; hazard ratio, 3.95; p=0.037), whereas LOH at 1p was not (p=0.786). Conclusion LOH at 16q was a significant negative prognostic factor affecting outcome in Korean pediatric FHWT patients. Due to the small sample size of this study, large-scale multicenter trials are warranted to investigate the prognostic value of LOH at 1p and 16q in Korean children with FHWT.
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PURPOSE The purpose of this study was to correlate the immunohistdegrees Chemical expressions of p53, p21 and bcl-2, with their loss of heterozygosity (LOH) and clinical significance. MATERIALS AND METHODS Paraffin-embedded tissue sections from 30 patients with gastric car cinomas were examined for immunohistdegrees Chemical staining and LOH study. Primary antibodies used in immunohistdegrees Chemical staining were mouse mondegrees Clonal antibody to human p53, p21/ WAF1 and bcl-2. For PCR-LOH assays, D6S271, D6S105, D18S386, TP53, D17S796, and D17S786 microsatellite markers were used. RESULTS The expression rates of p53, p21 and bcl-2 were 76.7%, 80% and 3.3%, respectively.
The expression of p21 was correlated with lymph node metastasis. LOH were found in 20.8% at D6S271, 42.3% at D6S105, 31.6% at D18S386, 39.1% at TP53, 40.9% at D17S796, and 50.0% at D17S786. No correlation was found between the immunohistdegrees Chemical expression and the LOH in these gene sites. CONCLUSION p53 and p21 were detected in high rate, whereas bcl-2 expression rate was very low in gastric adendegrees Carcinoma. Of them, overexpression of p21 was correlated with the tumor progression. High incidence rate of LOH may play an important role in gastric carcinogenesis.
These findings suggest that the effects on apoptosis and cell cycle by p53 and p21 were important in development and progression of gastric cancer.
PURPOSE Allelic deletion of p53 tumor suppressor gene have been observed frequently in a variety of human tumors. These losses are believed to contribute to the development of human cancers. But the loss of heterozygosity (LOH) data on chromosome 17p are rare and controversial with respect to cervical carcinomas. So, we tried to elucidate the frequency of p53 locus LOH in primary cervical carcinoma and compared the LOH data with clinicopathological parameters. MATERIALS AND METHODS In order to detect LOH within one of the well-known tumor suppressor gene, p53, three intragenic polymorphisms (exon 1, exon 4, and intron 6) and one microsatellite distal to the p53 gene (D17S5) were examined.
Paired DNA samples from 55 primary uterine cervical carcinomas and normal bloods were studied for the chromosomal allelic loss of p53 gene locus by polymerase chain reaction (PCR), the presence of human papilloma virus (HPV), and the presence of p53 gene point mutation by PCR-single conformation polymorphism (SSCP) analysis. And the relationships between allelic losses of this gene and conventional clinicopathological parameters were evaluated. RESULTS We could increase the heterozygosity of the p53 gene up to 1 (100%). The observed allelic loss rate of the p53 locus in informative cases was 5.5% (3/55) and the observed allelic loss rate of the D17S5 locus in informative cases was 8.7% (4/46) . Only one of the four patients with LOH at the D17S5 locus showed a concomittant allelic loss of the p53 gene. The overall LOH incidence of the chromosomal region comprising 17p13.1 (p53) to 17p13.3 (D13S5) was 10.9% (6/55). All the samples contained at least one of the oncogenic HPV type 16 and/or 18 sequences. No shifted bands were observed in the PCR-SSCP analysis of the p53 gene. The LOH of the p53 gene was not related to other parameters including clinical stage, histological type, and degree of differentiation. CONCLUSION Concerning with the results above, we conclude that the allelic imbalance of the p53 gene itself is not implicated as a major contributing factor in the malignant transformation or the tumor progression in HPV-positive cervical cancers. Another putative tumor suppressor gene which has more important function than p53 gene in cervical carcinogenesis might exist between these two loci [p53 (17p13.1) and D17S5 (17p13.3)].
Allelic deletions of tumor suppressor genes have been observed frequently in a variety of human tumors. These losses are believed to contribute to the development of human cancers. In order to detect loss of heterozygosity(LOH) within one of the well-known tumor suppressor gene, Rb(retinoblastoma), in primary uterine cervical cancers, we analysed four polymorphic intronic sites of Rb locus using polymerase chain reaction(PCR) in 55 primary cervical cancer tissues. The estimated heterozygote frequencies of intronl/BamHI, intronl7/XbaI, intron25/DraI, and intron 20 variable number of tandem repeat(VNTR) regions were 49%, 49%, 42%, and 80%, respectively. The observed frequencies of tumors with LOH at each locus were 21%(5 /24), 17%(5/29), 20%(5/20) and 44%(7/44) for intronl/BamHI, intronl7/XbaI, intron25/DraI and intron 20 VNTR polymorphic loci, respectively. The overall frequency of cervical cancer with at least one LOH at the Rb locus in this study was 14%(7/49), indicating that LOH at the Rb locus was not necessarily associated with cervical carcinogenesis. All the tumors showing LOH at the Rb locus were histologically moderatelv to poorly differentiated types and most of them(5 of the 7, 71%) were over FIGO stage II. These results suggest that the tumors with LOH at this locus may represent the general genomic instability which will contribute to the tumor progression and LOH of this gene may be used as one of the prognostic factors in cervical cancer in the future.