University of Texas, USA
Title: Tubal origination of â€œOvarianâ€ low-grade serous carcinoma: a gene expression profile study
Wenxin Zheng, M.D., tenure Professor of Pathology and Obstetrics and Gynecology, American board certified pathologist, director of the Gynecologic Pathology and Molecular Pathology program at the University of Arizona, graduated from Shanghai Medical College Fudan University and trained at Columbia University, Cornell University, and Brown University Medical Centers in anatomic pathology and gynecologic pathology. Dr. Zheng is an internationally recognized gynecologic pathologist with expertise in hormonal etiology of sporadic ovarian cancer, type II endometrial carcinogenesis, and hormone replacement therapy.
Background: Ovarian low-grade serous carcinomas (LGSC) are thought to evolve in a step-wise fashion from ovarian epithelial inclusions (OEI), serous cystadenomas (SC), and serous borderline tumors (SBT). Our previous study showed that the majority OEIs are derived from the fallopian tubal epithelia (FTE) rather than from ovarian surface epithelia (OSE). This study was designed to gain further insight into the cellular origin of LGSC by differential gene expression profiling studies.
Methods: Gene expression profiles were studied in 44 samples including 11 LGSCs, 7 SBTs, 6 SCs, 6 OEIs, 7 FTEs, and 6 OSEs. Correlation analyses of ovarian serous tumors including its precursor OEIs with FTE and OSE samples were performed by unsupervised hierarchical clustering. Rank-sum analyses and Pearson correlation tests were then applied to determine the likelihood of cellular origin of LGSC and its precursors. Final validation was done on selected genes and corresponding proteins.
Results: Gene expression profiles distinguish LGSC from OSE, but not from FTE cells. Furthermore, dendrograms produced by unsupervised hierarchical clustering showed ovarian serous tumors and OEIs were clustered closely in a branch, but separated from OSEs. After ascertaining the reliability of sequencing data, we found that OVGP1, WT-1, and FOM3 highly expressed in fallopian tube and OEI, and ovarian serous tumors, but not in OSE. In contrast, ARX and FNC1 were mainly expressed in OSE, but not in other studied samples.