Incidence of loss of heterozygosity at p53 and BRCA1 loci in serous surface carcinoma.
Serous surface carcinoma (SSC) is a neoplasm histologically indistinguishable from typical serous carcinomas that arise from the ovary but has a distinct clinical presentation. It is characterized by widespread peritoneal dissemination at presentation, but the ovaries are grossly normal in size and shape. If the carcinoma involves the ovaries microscopically, the tumor is confined to the surface or is minimally invasive. The recognition of this entity is important, because in some studies it appears to have a poorer prognosis than stage-matched serous cancers of the ovary. Loss of heterozygosity (LOH) of the p53 (17p) and BRCA1 (17q) tumor suppressor genes has been frequently identified in sporadic ovarian carcinomas. Although 17p LOH is correlated with common p53 gene mutations, inactivating mutations of the BRCA1 gene are uncommon in sporadic ovarian cases. In contrast, germline BRCA1 mutations are responsible for some hereditary forms of ovarian cancer, where it has been suggested that germline BRCA1 mutations confer a more favorable prognosis. In this study, 12 sporadic SSC were assessed for the presence of allelic deletions on the p53 and BRCA1 gene loci. DNA from both tumor and normal cells was obtained for LOH studies using tissue microdissection. Polymerase chain reaction (PCR) amplification was performed with the polymorphic DNA markers TP53 (17p13.1/p53 gene) and D17S579 (17q/BRCA1 gene). LOH in the p53 and BRCA1 loci was detected in 62.5% and 66.6% of the cases, respectively. In 50% of tumors informative for both markers, it is possible that an entire chromosome may be lost. In conclusion, we have shown that LOH of the p53 and BRCA1 loci is a frequent event in sporadic SSC, similar to what has been described in the usual form of serous ovarian carcinoma. Mutational analysis will be necessary to determine the exact role of these genes in this group of tumors.
Quezado
M M
MM
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Moskaluk
C A
CA
Bryant
B
B
Mills
S E
SE
Merino
M J
MJ
D002886:Chromosomes, Human, Pair 17; D003536:Cystadenocarcinoma / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D016158:Genes, p53; D006801:Humans; D019656:Loss of Heterozygosity; D010051:Ovarian Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction