title: Inhibitory role of prohibitin in human ovarian epithelial cancer.
abstract: OBJECTIVE
  To characterize the exact individual roles of gonadotropins on ovarian epithelial carcinogenesis, an earlier study showed that prohibitin was significantly up-regulated by luteinizing hormone (LH). To further clarify the role of prohibitin in ovarian carcinogenesis and its association with LH, herein we studied the expression of prohibitin in various ovarian tissues including different developmental stages of ovarian epithelial tumors.
  
  
  METHODS
  A total of 135 samples were studied by immunohistochemistry. These included benign ovarian cases with follicles, ovarian surface epithelia and ovarian epithelial inclusions (OEI) (n=30), serous cystadenoma (n=14), serous borderline tumor (n=12), serous carcinoma (n=20), mucinous cystadenoma (n=10), mucinous borderline tumor (n=10), mucinous carcinomas (n=10), endometrioid carcinomas (n=12), poorly/undifferentiated carcinomas (n=5), and fallopian tube (n=12).
  
  
  RESULTS
  Strong and diffuse staining of prohibitin was detected in luteinized ovarian stromal cells, follicular cells, fallopian tube, and OEI with serous differentiation. A significantly higher prohibitin expression in luteinized stromal cells than in non-luteinized stromal cells was observed (P<.01). Within the ovarian epithelium, the level of prohibitin expression was basically negative in ovarian surface epithelia, but highly expressed in OEI. However, compared to the level of prohibitin expression in OEI, it showed a trend of gradual loss from benign ovarian tumors, to borderline tumors and to carcinomas (P<.0001). Compared to the serous tumors, epithelial tumors with mucinous differentiation showed a significant lower level of prohibitin (P<.0001). An inverse correlation was noted between prohibitin expression and cancer grade. It is interesting to note that a high prohibitin expression level was seen in the fallopian tube, which is similar to OEI.
  
  
  CONCLUSIONS
  These data further suggest that prohibitin plays a tumor suppressing role, which is probably associated with LH mediated protection role against ovarian epithelial carcinoma. In addition to the tumor suppressive role of prohibitin, it also plays a role in cellular differentiation, which may be helpful to differentiate ovarian mucinous tumors from the tumors with serous differentiation in clinical settings. More importantly, our findings are supportive that the ovarian epithelial cancers, particularly the serous cancers including those precursors with serous differentiation are likely to be derived from fallopian tube instead of ovarian surface epithelia.
authors: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University Jinan, Shandong, 250012, China ; Department of Pathology, University of Arizona College of Medicine Tucson, AZ, 85724, USA.
authors: Lin
authors: L
authors: Jia
authors: Department of Endocrinology, Qilu Hospital, Shandong University Jinan, Shandong, 250012, China.
authors: Jian-Min
authors: JM
authors: Ren
authors: Department of Obstetrics and Gynecology, Henan Province People's Hospital Zhengzhou, Henan, 450003, China.
authors: Yi-Ying
authors: YY
authors: Wang
authors: Shanghai Jiai Genetics & IVF Institute, Hospital of Obstetrics and Gynecology, Fudan University Shanghai, 200090, China.
authors: Yu
authors: Y
authors: Zheng
authors: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University Jinan, Shandong, 250012, China.
authors: Hui
authors: H
authors: Zhang
authors: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University Jinan, Shandong, 250012, China.
authors: Qing
authors: Q
authors: Zhang
authors: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University Jinan, Shandong, 250012, China.
authors: Bei-Hua
authors: BH
authors: Kong
authors: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University Jinan, Shandong, 250012, China ; Department of Pathology, University of Arizona College of Medicine Tucson, AZ, 85724, USA ; Department of Obstetrics and Gynecology, University of Arizona Tucson, AZ, 85724, USA ; Arizona Cancer Center, University of Arizona Tucson, AZ, 85724, USA.
authors: Wen-Xin
authors: WX
authors: Zheng
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000737:chemistry* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D018269:Carcinoma, Endometrioid / Q000737:chemistry* / Q000473:pathology; D000077216:Carcinoma, Ovarian Epithelial; D002454:Cell Differentiation; D019070:Cell Lineage; D018291:Cystadenoma, Mucinous / Q000737:chemistry* / Q000473:pathology; D018293:Cystadenoma, Serous / Q000737:chemistry* / Q000473:pathology; D005187:Fallopian Tubes / Q000737:chemistry / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000473:pathology; D000091402:Prohibitins; D012097:Repressor Proteins / Q000032:analysis*; D017154:Stromal Cells / Q000737:chemistry / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D000091402:Prohibitins; D012097:Repressor Proteins
keywords: Gonadotropin; luteinizing hormone; ovarian cancer; prohibitin