Abstract LB-271: Benign ovarian serous tumors: A redefining moment

Abstract

Abstract Ovarian cancer is a very significant health burden and the fifth leading cause of cancer death in women. At the time of diagnosis, women often have advanced disease and as a consequence their prognosis is extremely poor. Our understanding of the progression of ovarian cancer through precursor stages and the molecular genetic events underlying these changes is currently limited. Although a number of candidate precursor lesions have been identified it remains to confirm the true contribution of these precursor lesions to the onset of ovarian cancer. Epithelial tumors account for 70–80% of all ovarian tumors and the serous subtype accounts for approximately 53% of ovarian epithelial tumors. Serous cystadenomas and cystadenofibromas are common ovarian lesions, accounting for 25% of all benign ovarian tumors and 58% of the ovarian serous tumors. Although there is little definitive molecular or histopathological evidence, ovarian serous cystadenomas and cystadenofibromas have been presumed by many to be the precursor lesions to serous borderline tumors and low grade serous carcinomas. Using the ultra high-resolution Affymetrix SNP6.0 microarray (>1.8M probes) and the high-resolution Molecular Inversion Probe (MIP) assay (>330k probes) we performed copy number (CN) and loss of heterozygosity analysis on 14 ovarian serous cystadenomas and 20 ovarian serous cystadenofibromas. Each tumour was microdissected to allow analysis of tumour epithelium and adjacent stroma with matching lymphocyte DNA for each case. CN alterations were only detected in the epithelial component in 2 of 34 cases (5.9%) but surprisingly alterations were seen in 35% of the stromal components (2/14 cystadenomas and 10/20 cystadenofibromas). Notably, 9/12 of these cases carried a chromosome 12 gain, which has been previously identified as characteristic of the fibroma-thecoma group of ovarian stromal tumors. One of 34 cases (2.9%) was biphasic with CN alterations in both the epithelium and stroma. The lack of identifiable CN alterations or KRAS and BRAF mutations in the epithelium of the vast majority of the ovarian serous cystadenomas and cystadenofibromas supports the notion that these lesions have limited neoplastic potential. These findings are consistent with the predictions of Seidman and Mehrotra (2005) that the majority of benign ovarian serous tumors are potentially cystically dilated glandular inclusions and misclassified fibromas with epithelial inclusions. This would considerably deflate the frequency of the serous subtype within ovarian epithelial tumors and alter the significance of the other epithelial subtypes, with compelling implications for studies of serous ovarian “precursor” lesions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-271. doi:10.1158/1538-7445.AM2011-LB-271