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

Diagn Cytopathol. 2001 May;24(5):328-32. doi: 10.1002/dc.1070.


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.

MeSH terms

  • Adenocarcinoma, Clear Cell / genetics*
  • Adenocarcinoma, Clear Cell / pathology
  • Adenocarcinoma, Clear Cell / secondary*
  • Biomarkers, Tumor
  • Chromosomes, Human, Pair 3 / genetics*
  • Diagnosis, Differential
  • Dissection*
  • Female
  • Genes, Tumor Suppressor / genetics
  • Humans
  • Ligases*
  • Loss of Heterozygosity / genetics*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / secondary*
  • Polymerase Chain Reaction*
  • Proteins / genetics
  • Retrospective Studies
  • Tumor Suppressor Proteins*
  • Ubiquitin-Protein Ligases*
  • Von Hippel-Lindau Tumor Suppressor Protein


  • Biomarkers, Tumor
  • Proteins
  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligases
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Ligases
  • VHL protein, human