Chromosomal instability in fallopian tube precursor lesions of serous carcinoma and frequent monoclonality of synchronous ovarian and fallopian tube mucosal serous carcinoma

Abstract

Objectives Pelvic serous carcinomas are classified according to the location of greatest mass of tumor as ovarian, peritoneal or fallopian tube. Recent studies suggest these cancers may arise in the fallopian tube. This study explores the relationship between ovarian cancers and fallopian tube mucosal involvement. Methods Sixteen consecutive cases of epithelial ovarian malignancy were prospectively identified and the fallopian tubes submitted in toto for histopathological examination for tubal mucosal involvement. Immunohistochemical staining for p53 and Ki-67, and fluorescent in situ hybridization (FISH) analysis for chromosomal copy number changes were performed on 10 cases. Three cases of mucosal epithelial abnormalities identified in risk-reducing salpingectomy specimens were similarly characterized. Results Of sixteen cases, twelve were high-grade serous carcinoma, stage III, and four cases were stage I, two borderline mucinous, one borderline serous, and one low-grade mucinous carcinoma. Ten cases of high-grade serous carcinoma showed either unilateral fallopian tube mucosal involvement ( n = 7) or tubal obliteration ipsilateral to the dominant ovarian mass ( n = 3), compared to none of the other carcinomas. FISH analysis showed similar copy number changes in the ovarian and fallopian tube mucosal carcinoma in 3 cases, suggesting a unifocal origin; one case had differences suggesting multifocal origin of cancer. One case had equivocal FISH results. From risk-reducing salpingectomy cases, the multiple foci of tubal intraepithelial carcinoma and focus of invasive carcinoma showed similar gene copy number changes within each case, suggesting monclonality. Both cases of epithelial atypia/dysplasia showed gene copy number changes. Conclusions Fallopian tube mucosal and ovarian tumors have similar genetic abnormalities in most cases, indicating a monoclonal origin that may originate either from the ovary, peritoneum or fallopian tube. In situ epithelial lesions of the fallopian tube from risk-reducing salpingectomies show gene copy abnormalities consistent with these being early lesions of serous carcinoma and suggest that chromosomal instability is a very early event in serous carcinogenesis.