TY - JOUR
T1 - Tubal origin of ovarian low-grade serous carcinoma
AU - Li, Jie
AU - Abushahin, Nisreen
AU - Pang, Shujie
AU - Xiang, Li
AU - Chambers, Setsuko K.
AU - Fadare, Oluwole
AU - Kong, Beihua
AU - Zheng, Wenxin
N1 - Funding Information:
Dr Jie Li is a PhD candidate co-trained at University of Arizona, USA and Shandong University, China. The project was supported in part by Better Than Ever Fund, P30 CA23074 from Arizona Cancer Center and Department of Pathology, University of Arizona Startup fund to WZ, and Shandong University, China.
PY - 2011/11
Y1 - 2011/11
N2 - Ovarian low-grade serous carcinomas are thought to evolve in a stepwise fashion from ovarian epithelial inclusions, cystadenomas, and borderline tumors. The current study was designed to gain insight into the origins of low-grade serous carcinomas (tubal versus ovarian) by comparatively evaluating the morphologic (secretory and ciliated cell distribution) and immunophenotypic (using antibodies to PAX8, tubulin, calretinin, and Ki67) attributes of its putative precursor lesions, the normal tubal epithelium, and the overt malignancy. A total of 226 adnexal tissues from 178 patients were studied, including 98 adnexae removed for non-neoplastic indications, 48 serous cystadenomas, 42 serous borderline tumors, and 38 low-grade serous carcinomas. Normal distal tubal epithelium comprised an admixture of PAX8/tubulin secretory cells and PAX8/tubulin ciliated cells with a proliferative index of ∼3%. The vast majority of ovarian surface epithelia displayed a mesothelial phenotype (calretinin/PAX8/tubulin) and low proliferative index (0% (12 per 1000)), although 4% of cases also displayed foci with tubal phenotype (calretinin/PAX8/tubulin). In contrast, most (78%) of the ovarian epithelial inclusions displayed a tubal phenotype and had a significantly higher proliferative index (1%) than ovarian surface epithelium, indicating that in most cases, the ovarian surface epithelium and ovarian epithelial inclusions are of different lineages. There was a progressive decrease in the population of ciliated cells, as evidenced by increasing secretory/ciliated cell ratio, from ovarian epithelial inclusions/cystadenomas to borderline tumors to low-grade serous carcinoma, indicating that the latter is a clonal expansion of secretory cells. Overall, the findings make a strong argument that the ovarian epithelial inclusions with a tubal phenotype is likely derived from fallopian tube through an intraovarian endosalpingiosis rather than through Mullerian metaplasia from ovarian surface epithelium. Genetic and molecular studies are needed to further confirm this finding as tubal origination of ovarian serous cancers will have a significant impact on ovarian cancer prevention and management.
AB - Ovarian low-grade serous carcinomas are thought to evolve in a stepwise fashion from ovarian epithelial inclusions, cystadenomas, and borderline tumors. The current study was designed to gain insight into the origins of low-grade serous carcinomas (tubal versus ovarian) by comparatively evaluating the morphologic (secretory and ciliated cell distribution) and immunophenotypic (using antibodies to PAX8, tubulin, calretinin, and Ki67) attributes of its putative precursor lesions, the normal tubal epithelium, and the overt malignancy. A total of 226 adnexal tissues from 178 patients were studied, including 98 adnexae removed for non-neoplastic indications, 48 serous cystadenomas, 42 serous borderline tumors, and 38 low-grade serous carcinomas. Normal distal tubal epithelium comprised an admixture of PAX8/tubulin secretory cells and PAX8/tubulin ciliated cells with a proliferative index of ∼3%. The vast majority of ovarian surface epithelia displayed a mesothelial phenotype (calretinin/PAX8/tubulin) and low proliferative index (0% (12 per 1000)), although 4% of cases also displayed foci with tubal phenotype (calretinin/PAX8/tubulin). In contrast, most (78%) of the ovarian epithelial inclusions displayed a tubal phenotype and had a significantly higher proliferative index (1%) than ovarian surface epithelium, indicating that in most cases, the ovarian surface epithelium and ovarian epithelial inclusions are of different lineages. There was a progressive decrease in the population of ciliated cells, as evidenced by increasing secretory/ciliated cell ratio, from ovarian epithelial inclusions/cystadenomas to borderline tumors to low-grade serous carcinoma, indicating that the latter is a clonal expansion of secretory cells. Overall, the findings make a strong argument that the ovarian epithelial inclusions with a tubal phenotype is likely derived from fallopian tube through an intraovarian endosalpingiosis rather than through Mullerian metaplasia from ovarian surface epithelium. Genetic and molecular studies are needed to further confirm this finding as tubal origination of ovarian serous cancers will have a significant impact on ovarian cancer prevention and management.
KW - PAX8
KW - cortical inclusion cysts
KW - endosalpingiosis
KW - fallopian tube
KW - ovarian epithelial inclusions
KW - ovarian serous carcinoma
UR - http://www.scopus.com/inward/record.url?scp=80455174018&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80455174018&partnerID=8YFLogxK
U2 - 10.1038/modpathol.2011.106
DO - 10.1038/modpathol.2011.106
M3 - Article
C2 - 21701538
AN - SCOPUS:80455174018
SN - 0893-3952
VL - 24
SP - 1488
EP - 1499
JO - Modern Pathology
JF - Modern Pathology
IS - 11
ER -