Cellular Plasticity of Tubal and Ovarian Surface Epithelium: The Mixed Mesothelial-Mullerian Phenotype
Michael Herman Chui. Toronto General Hospital, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada
Background: There is accumulating evidence that the majority of high-grade serous carcinomas originate from the distal fallopian tube (FT), and several recent studies have suggested a similar model for low-grade serous neoplasms. There are however, serous carcinomas that bear striking resemblance, by morphology and immunoprofile, to epithelioid mesothelioma, suggesting that the cell of origin is capable of mesothelial differentiation. The purpose of this study is therefore to identify the process of transdifferentiation of ovarian surface epithelium (OSE) to Mullerian epithelium in salpingo-oophorectomy specimens.
Design: The distribution and intensity of immunostaining for Mullerian epithelial markers (E-cadherin, CA-125) and the mesothelial marker calretinin were analyzed in the distal FT and OSE in salpingo-oophorectomy specimens with epithelial inclusion cysts, serous cystadenoma, salpingitis or serous borderline tumour.
Results: In the OSE, the majority of flat/cuboidal cells exhibit a mesothelial phenotype (calretinin+/E-cad-/CA125-), with focal positivity for E-cadherin and CA-125. Columnar epithelium within cortical clefts and surface papillomatosis show a mixed mesothelial/Mullerian phenotype (calretinin+/E-cad+/CA125+). Cystic lesions, lined by ciliated or flat/cuboidal epithelium, may be composed of cells with Mullerian, mesothelial, or mixed immunoprofiles. Occasional calretinin+ cells are often present in the distal FT. Strong calretinin staining may be observed in the setting of salpingitis.
Figure 1: Strong calretinin positivity in serous borderline tumour, suggestive of origin from OSE (a); and in distal FT with acute salpingitis (b). CA-125 staining in cortical inclusion cyst lined by tubal-type epithelium and adjacent OSE (c), and in surface papillomatosis (d).
Conclusions: The OSE is capable of partial Mullerian epithelial transdifferentiation, whereas reactive FT epithelium can exhibit features of mesothelium, consistent with a transitional zone of differentiation at the tubal-ovarian junction. These preliminary results suggest that at least some serous ovarian tumors could originate via Mullerian metaplasia of the OSE.
Category: Gynecologic & Obstetrics
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 177, Wednesday Morning