Different proportions of aneusomic cells in ovarian inclusion cysts associated with serous borderline tumours and serous high-grade carcinomas support different pathogenetic pathways.

Ovarian serous tumours may arise from the ovarian surface epithelium or from ovarian cortical epithelial inclusion cysts. However, little is known about the pathogenetic mechanisms involved in the progression from ovarian surface epithelium or inclusion cysts to neoplastic disease. In the present study, chromosomal aberrations typical of ovarian serous tumours were studied in ovarian surface epithelium and inclusion cysts. Ten ovaries with inclusion cysts obtained from patients without a gynaecological tumour, as well as 15 serous borderline tumours and 16 invasive high-grade serous carcinomas with inclusion cysts either in the ipsi- or in the contralateral ovary, were investigated by fluorescence in situ hybridization (FISH) using centromere enumeration probes directed against chromosomes 1, 6, 7, and X. The proportions of aneusomic cells were assessed. Trisomies 1 and 7 and monosomies 6 and X were present in the surface epithelium, inclusion cysts, and tumours, providing evidence for a link between the surface epithelium, and inclusion cysts, and serous neoplasia. Inclusion cysts generally harboured more aneusomic cells than the associated surface epithelium, suggesting an influence of the ovarian stroma on the development of chromosomal instability. Moreover, inclusion cysts associated with borderline tumours displayed a higher proportion of aneusomic cells than inclusion cysts associated with invasive high-grade carcinoma and than inclusion cysts in ovaries without neoplastic disease. These results suggest a genetic field defect of the inclusion cyst epithelium in serous borderline tumours. Invasive high-grade serous carcinomas, by contrast, may arise from single cell clones subject to a different set of genetic events.