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Origin of ovarian epithelial inclusions and its relationship with the development of low-grade serous carcinoma

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Author:
No author available
Journal Title:
Chinese Journal of Obstetrics and Gynecology
Issue:
10
DOI:
10.3760/cma.j.issn.0529-567x.2011.10.003
Key Word:
卵巢;包涵体;卵巢肿瘤;囊腺癌;浆液;成对盒转录因子类;Ovary;Inclusion bodies;Ovarian neoplasms;Cystadenocarcinoma,serous;Paired box transcription factors

Abstract: Objective To investigate the possible origin of ovarian epithelial inclusions and its relationship with the low-grade ovarian serous carcinoma.Methods By comparatively evaluating the morphologic (secretory and ciliated cell distribution ) and immunophenotypic [using paired box gene 8 (PAX8),tubulin,calretinin,and Ki-67 as first antibodies] attributes of ovarian epithelial inclusions,the normal tubal epithelium,and the ovarian tumors,all adnexal tissues from a total of 198 patients were studied,including 116 adnexae removed for non-neoplastic indications,53 serous cystadenomas,44 serous borderline tumors,and 41 low-grade serous carcinomas,which were collected from Qilu Hospital of Shandong University and University of Arizona in USA.Immunohistochemical single staining was used to detect the expressions of PAX8,tubulin,calretinin,and Ki-67 in the two groups,while immunohistochemical double staining of PAX8/calretinin was used to figure out the immunophenotype of various ovarian epithelial inclusions in a more intuitive way.Results With immunohistochemical single staining of PAX8 and calretinin,the vast majority (90%,54/60) of ovarian surface epithelia displayed a mesothelial phenotype [calretinin(+),PAX8 (-)],whereas 10% (6/60)of the cases displayed foci with tubal phenotype [calretinin(-),PAX8 (+)].In contrast,most (79%,728/921 ) of the ovarian epithelial inclusions displayed a tubal phenotype,though 21% (193/921) of the ovarian epithelial inclusions showed a mesothelial phenotype.It was further proved by immunohistochemical double staining of PAX8/ calretinin.Secretory and ciliated cells were found in the ovarian epithelial inclusions with tubal phenotype.There was a progressive increase in the secretory/ciliated cells ratio and proliferative index,from ovarian epithelial inclusions/cystadenomas to borderline tumors to low-grade serous carcinoma,according to the expression of tubulin and Ki-67.Conclusions The findings make a strong argument that the ovarian epithelial inclusions displaying a tubal phenotype with PAX8 (+),calretinin (-) is likely derived from fallopian tube rather than through Mullerian metaplasia from ovarian surface epithelium.The increasing trend of secretory/ciliated cells ratio and proliferative index from ovarian epithelial inclusions/cystadenomas to borderline tumors to low-grade serous carcinoma indicates that the latter is a clonal expansion of secretory cells.Genetic and molecular studies are needed to further confirm these findings.

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