Ovarian Cancer Risk Assessment Via Expression Profiling of the Distal Fallopian Tube Epithelium
W Xian, KK Mehra, V Vathipadiekal, SW Tay, M Birrer, CP Crum. Brigham and Women's Hospital, Boston, MA; Massachusetts General Hospital, Boston, MA; Institute of Molecular Biology, Singapore, Singapore
Background: Risk of ovarian cancer is associated with inherited mutations in the BRCA1 or BRCA2 genes; however, this group accounts for only 10% of the ovarian cancer population and the factors that would distinguish the remaining 90% of women are not known. Recently, the distal fallopian tube has been proposed as a site of origin for a significant subset of ovarian cancers, specifically high grade serous carcinomas, and a serous carcinogenic sequence has been described in this site. This study addressed the hypothesis that the benign appearing distal fallopian tube epithelium of women with high grade serous carcinomas is fundamentally different from the background population of lower risk individuals.
Design: Ten cases each of high-grade pelvic serous carcinoma and benign disorders (ovarian fibroma, mucinous cystadenoma) were selected. Frozen fimbrial sections from each case were sectioned and RNA isolated by laser capture microdissection. RNA was amplified, hybridized to Affymetrix U133 genechips and the resulting data resolved by Partek Genomics Suite software and Ingenuity Pathway Analysis software.
Results: A supervised comparison using Partek software identified 558 genes expressed at more than or equal to 2 fold different levels (P<0.05) in benign fimbrial epithelium associated with high-grade pelvic serous carcinoma vs benign disorders. Moreover, analysis revealed important pathways that might cooperate with the p53 pathway to regulate serous carcinoma development and progression. Currently, pathway specific PCR array is being used to validate this finding in larger pool of samples and will be discussed.
Conclusions: This study has revealed, for the first time, that differences in gene expression might distinguish normal distal fallopian tubes from women with serous cancer and controls. This approach offers the potential for identifying unique gene pathways that can be employed, singly or in aggregate, to identify greater ovarian cancer risk and underscores the distal fallopian tube as a potential surrogate for ovarian cancer risk assessment.
Category: Gynecologic & Obstetrics
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 142, Tuesday Afternoon