EVIDENCE FOR THE MULTIFOCAL ORIGIN OF BILATERAL AND ADVANCED HUMAN SEROUS BORDERLINE OVARIAN-TUMORS

Borderline ovarian turners (BOTs), or ovarian tumors of low malignant potential, represent a distinct category of epithelial ovarian neoplas ms that have a clinically more favorable outcome than invasive epithel ial ovarian cancer. Histologically, BOTs and invasive ovarian carcinom as both show cellular proliferation and pleomorphism, but unlike invas ive ovarian carcinomas, BOTs lack stromal invasion. Although serous BO TS are frequently confined to a single ovary at the time of diagnosis, bilateral or extra-ovarian spread occurs in 30-40% of cases, The purp ose of this study is to determine whether bilateral or extraovarian se rous borderline lesions are metastatic sites from the original tumor, or represent separate primary tumors, DNA specimens from multiple tumo r sites and normal tissue controls were obtained in eight women with b ilateral or extra-ovarian serous borderline turners. The pattern of lo ss of heterozygosity at the androgen receptor locus on the X chromosom e was evaluated in the multiple tumor sites. Tn addition, the pattern of X-chromosome inactivation was determined using HpaII restriction en donuclease digestion, followed by PCR amplification of the androgen re ceptor locus, Multifocality, was determined when alternate patterns of X-chromosome inactivation occurred, In two of the eight patients, the left and right ovarian tumor sites had different androgen receptor al leles inactivated, indicating that the bilateral tumors derived indepe ndently. In a third patient, the TF, inactivation pattern in the left ovarian tumor differed from the two peritoneal implants, suggesting th at the implants were separate primary tumors, and not metastatic, from the left ovarian tumor, The remaining five patients had the same patt ern of loss of heterozygosity and X inactivation in the tumor sites st udied, These results suggest that bilateral and advanced stage serous BOTs may be multifocal in origin, This result is in contrast to invasi ve epithelial ovarian cancer, which has been shown to be unifocal in o rigin.