Molecular Evidence for Multifocal Papillary Serous Carcinoma of the Peritoneum in Patients With Germline BRCA1 Mutations

• Published in: JNCI : Journal of the National Cancer Institute Vol. 90; no. 11; pp. 841 - 845
• Main Authors: Schorge, John O., Muto, Michael G., Welch, William R., Bandera, Christina A., Rubin, Stephen C., Bell, Debra A., Berkowitz, Ross S., Mok, Samuel C.
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 03-06-1998; Oxford Publishing Limited (England)
• Subjects: Abdomen; Adult; Aged; Aged, 80 and over; Alleles; Biological and medical sciences; Biomarkers, Tumor - genetics; Clone Cells - ultrastructure; Cystadenocarcinoma, Papillary - genetics; Cystadenocarcinoma, Papillary - pathology; Disease Susceptibility; DNA Methylation; DNA, Neoplasm - genetics; Dosage Compensation, Genetic; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genes, BRCA1; Genes, p53; Genetic Markers; Genetics; Humans; Loss of Heterozygosity; Medical research; Medical sciences; Middle Aged; Molecular biology; Mutation; Neoplastic Stem Cells - ultrastructure; Neoplastic Syndromes, Hereditary - genetics; Neoplastic Syndromes, Hereditary - pathology; Ovarian cancer; Ovariectomy; Ovary - embryology; Peritoneal Neoplasms - genetics; Peritoneal Neoplasms - pathology; Peritoneum - embryology; Receptors, Androgen - genetics; Retrospective Studies; Trinucleotide Repeats; Tumors; X Chromosome - genetics; Human; Papillary carcinoma; Androgen; Abdominal disease; Exploration; Malignant tumor; Mutation; Peritoneum; Hormonal receptor
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/90.11.841

Papillary serous carcinoma of the peritoneum (PSCP) diffusely involves peritoneal surfaces, while it spares or only superficially involves the ovaries. PSCP is histologically indistinguishable from serous epithelial ovarian carcinoma, and it may develop years after oophorectomy. The molecular pathogenesis of PSCP remains unresolved, although preliminary data suggest a multifocal origin in some cases. Patients with germline BRCA1 mutations may develop PSCP in addition to breast and ovarian carcinomas. The purpose of this study was to utilize the androgen receptor (AR) gene locus to test the hypothesis that some cases of PSCP have a multifocal origin and to determine if patients with germline BRCA1 mutations develop multifocal PSCP.
Specimens of normal and tumor tissues from 22 women with PSCP were obtained, and DNA was extracted. The AR gene locus was evaluated for patterns of loss of heterozygosity (LOH) and X-chromosome inactivation. The methylation-sensitive Hpa II restriction enzyme was used to differentiate the active and inactive X chromosomes. Germline BRCA1 mutation status of the patients was determined previously.
Genetic analysis of tumor specimens indicated that five (23%) of 22 case subjects had patterns of selective LOH at the AR locus, consistent with multifocal, polyclonal disease origin. Two patients with selective LOH also had alternating X-chromosome inactivation patterns. Patients with germline BRCA1 mutations were more likely to have evidence of multifocal disease (two-sided Fisher's exact test, P = .01).
Our results show that PSCP has a multifocal origin in at least some cases. Furthermore, patients with germline BRCA1 mutations are more likely to develop multifocal PSCP than are patients without BRCA1 mutations.