title: Tubal origin of ovarian endometriosis.
abstract: Endometriosis is a puzzling and debilitating disease that affects millions of women around the world. Ovary is the most common organ site involved by endometriosis. Despite various hypotheses about its cell of origin, uncertainty remains. On the basis of our clinicopathologic observations, we hypothesize that fallopian tube may contribute the histogenesis of ovarian endometriosis. To examine if the hypothesis, tubal origin of ovarian endometriosis, has scientific supporting evidence, we identified a set of novel genes, which are either highly expressed in the normal fallopian tube or in the endometrium through a gene differential array study. Among many differentially expressed genes, FMO3 and DMBT1 were selected as the initial biomarkers to test the hypothesis. These biomarkers were then validated in ovarian sections with foci of endometriosis by comparing their expression levels in the fallopian tube and the endometrium within the same patients with real-time PCR, western blot and immunohistochemistry analysis. FMO3 was highly expressed in the tubal epithelia while low in the paired endometrium. In contrast, DMBT1 was high in the endometrium but low in the fallopian tube. In 32 ovarian endometriosis cases analyzed by real-time PCR, 18 (56%) showed a high level of FMO3 and a low level of DMBT1 expression. However, 14 (44%) endometriosis cases showed a reversed expression pattern with these two markers. Results were similarly seen in the methods of western blot and immunohistochemistry. The findings suggest that approximately 60% of the ovarian endometriosis we studied may be derived from the fallopian tube, whereas about 40% of the cases may be of endometrial origin. The fallopian tube epithelia may represent one of the tissue sources contributing to ovarian endometriosis. Such novel findings, which require confirmation, may have a significant clinical impact in searching for alternative ways of prevention and treatment of endometriosis.
authors.affiliation: 1] Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Shandong, China [2] Key Laboratory of Gynecologic Oncology, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Shandong, China [3] Department of Pathology, University of Arizona College of Medicine, Tucson, AZ, USA.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: 1] Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Shandong, China [2] Key Laboratory of Gynecologic Oncology, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Shandong, China [3] Department of Pathology, University of Arizona College of Medicine, Tucson, AZ, USA.
authors.forename: Lijie
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, University of Arizona College of Medicine, Tucson, AZ, USA.
authors.forename: Yiying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shandong University School of Medicine, Shandong, China.
authors.forename: Tingguo
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Shandong University School of Medicine, Shandong, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: 1] Department of Obstetrics and Gynecology, University of Arizona, Tucson, AZ, USA [2] Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Janiel M
authors.initials: JM
authors.lastname: Cragun
authors.affiliation: 1] Department of Obstetrics and Gynecology, University of Arizona, Tucson, AZ, USA [2] Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Setsuko K
authors.initials: SK
authors.lastname: Chambers
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Shandong, China.
authors.forename: Beihua
authors.initials: B
authors.lastname: Kong
authors.affiliation: 1] Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Shandong, China [2] Department of Pathology, University of Arizona College of Medicine, Tucson, AZ, USA [3] Department of Obstetrics and Gynecology, University of Arizona, Tucson, AZ, USA [4] Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002135:Calcium-Binding Proteins; D019070:Cell Lineage; D004268:DNA-Binding Proteins; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000737:chemistry / Q000473:pathology*; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology*; D005187:Fallopian Tubes / Q000737:chemistry / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010049:Ovarian Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010105:Oxygenases / Q000032:analysis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics; D025521:Tumor Suppressor Proteins
chemical_list: D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)