title: Endometrial BCL6 Overexpression in Eutopic Endometrium of Women With Endometriosis.
abstract: The objective of this study was to examine B-cell CLL/lymphoma 6 (BCL6) expression in human eutopic endometrium across the menstrual cycle in women with and without endometriosis and to establish a cutoff for future studies. This design was a series of case-control studies in tertiary University teaching hospitals. We examined BCL6 expression by messenger RNA and immunohistochemically in prospectively collected samples in both the proliferative (P) and the secretory phases. BCL6 is minimally increased in the mid-secretory phase of the menstrual cycle compared to the P phase in normal patients. BCL6 protein expression was significantly higher in the secretory phase of patients with endometriosis (n = 29) versus fertile controls without endometriosis at laparoscopy (n = 20; P < .0001). Normal fertile controls (n = 28) recruited for endometrial biopsy also had low levels of secretory phase BCL6 expression compared to women with unexplained infertility (UI; n = 119). A receiving-operator characteristic analysis of these data revealed an area under the curve of 94% (95% confidence interval 85%-100%; P < .0001) with an HSCORE cutoff of 1.4 to differentiate cases with and without endometriosis. Using this cutoff value, BCL6 was positive in 88% of cases with UI. Laparoscopic examination of a subset of 65 patients confirmed abnormalities in 98% of cases; 61 (93.8%) were found to have endometriosis, 3 (4.6%) with hydrosalpinx, and 1 (1.5%) with a normal pelvis. These data suggest that BCL6 is a promising candidate as a single diagnostic biomarker for detection of endometriosis in women with otherwise UI and may be associated with endometrial dysfunction, including progesterone resistance.
authors.affiliation: Obstetrics and Gynecology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA Obstetrics and Gynecology, Carilion Clinic, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Evans-Hoeker
authors.affiliation: Obstetrics and Gynecology, Greenville Health System, Greenville, SC, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Lessey
authors.affiliation: Obstetrics, Gynecology and Reproductive Biology of Michigan State University, Grand Rapids, MI, USA Department of Women's Health, Spectrum Health System, Grand Rapids, MI, USA.
authors.forename: Jae Wook
authors.initials: JW
authors.lastname: Jeong
authors.affiliation: Departamento de Ginecologia e Obstetricia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Ricardo F
authors.initials: RF
authors.lastname: Savaris
authors.affiliation: Institute for Maternal and Child Research, University of Chile, Santiago, Chile.
authors.forename: Wilder A
authors.initials: WA
authors.lastname: Palomino
authors.affiliation: Obstetrics and Gynecology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Lingwen
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Pathology Associates, Greenville Health System, Greenville, SC, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Schammel
authors.affiliation: Obstetrics and Gynecology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA youngs@med.unc.edu.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Young
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D004715:Endometriosis / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000175:diagnosis / Q000378:metabolism; D008597:Menstrual Cycle; D011446:Prospective Studies; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C084103:BCL6 protein, human; D015415:Biomarkers; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger
keywords: BCL6; biomarker; endometriosis; endometrium; infertility