Detection of loss of heterozygosity at chromosome 3p25–26 in primary and metastatic ovarian clear‐cell carcinoma: Utilization of microdissection and polymerase chain reaction in archival tissues

Abstract

Loss of heterozygosity (LOH) at the 3p region is found in up to 50% of epithelial ovarian neoplasms. The von Hippel-Lindau (VHL) gene at the 3p25 locus is one of the tumor-suppressor genes located at 3p. The role, if any, of the VHL gene locus is not clear in ovarian carcinogenesis. We analyzed primary and metastatic ovarian clear-cell carcinomas (OCCC) for LOH at 3p25 to determine its frequency and its diagnostic utility as an adjunctive tool in the differential diagnosis of metastatic clear-cell carcinomas. Microdissection followed by single-step DNA extraction and polymerase chain reaction (PCR) amplification, using two polymorphic markers flanking the VHL gene locus, was done on archival histology and cytology samples from 9 patients with metastatic OCCC. Of the informative cases, 43% of the metastatic and 50% of the primary OCCC showed LOH. LOH at the VHL gene locus is not uncommon in clear-cell ovarian carcinoma. LOH at 3p25 in cytologic specimens may be a valuable adjunct in the diagnosis of OCCC metastasis in cytologically equivocal cases. OCCC should enter the differential in clear-cell carcinomas of unknown primary that show LOH at 3p25. Published 2001 Wiley-Liss, Inc.

Expression and regulation of tumor necrosis factor α in normal and malignant ovarian epithelium

“…Furthermore, our studies of TNF-a mRNA decay indicate that posttranscriptional regulation is an important mechanism underlying ovarian tumor cell TNF-a production. In renal cancer, the von Hippel-Lindau mutation (also described in clear cell carcinoma of the ovary) is causally linked to increased TNF-a expression via derepression of mRNA translation (26,27). TNF-a also regulated the stability of TNF-a mRNA as well as CXCL8 and vascular endothelial growth factor mRNA in glioma cells (28).…”

Epithelial cancer in Fanconi anemia complementation group D2 (Fancd2) knockout mice

“…Importantly, some cases of familial ovarian cancer have been linked precisely to the region where FANCD2 resides in the human genome (Sekine et al 2001;Simsir et al 2001;Zhang and Xu 2002). Future studies of human patients with these disorders will be needed to determine whether FA genes play a role in sporadic or inherited human cancers.…”

An allelotype analysis indicating the presence of two distinct ovarian clear-cell carcinogenic pathways: endometriosis-associated pathway vs. clear-cell adenofibroma-associated pathway

“…Therefore, to clarify whether differences in genetic background underline the two possible carcinogenic pathways to ovarian clear-cell adenocarcinoma (endometriosisassociated pathway vs. CCAF-associated pathway), we performed polymerase chain reaction (PCR)-based LOH analyses using 24 polymorphic markers located on 12 chromosomal arms where relatively frequent LOH has been reported in ovarian epithelial tumors, including clear-cell adenocarcinoma or endometriosis [15][16][17][24][25][26][27][28][29][30][31]. We then compared the allelic patterns of carcinomas with putative distinct precursors, since demonstrating the presence or absence of divergent carcinogenic pathways in ovarian clear-cell adenocarcinoma will provide insight into the genetic origin of this tumor.…”