title: Impact and mechanistic role of oral contraceptive pills on the number and epithelial type of ovarian cortical inclusion cysts; a clinicopathology and immunohistochemical study.
abstract: BACKGROUND
  Ovarian epithelial cancers are among the most lethal women's cancers. There is no doubt about the preventive role of oral contraceptive pills (OCPs) in development of ovarian cancers. But, there are limited numbers of studies to address the effect of these agents on the number of cortical inclusion cysts (CICs), their epithelial type and suppression of the metaplastic phenomenon by these pills. The aim of this study was to clarify the role of these agents in the prevention of these cyst formation and tubal metaplasia and also examine the mesenchymal-epithelial transition theory in this context by immunohistochemical methods.
  
  
  METHODS
  The representative section(s) of ovarian cortex from a total number of 201 consecutive total abdominal hysterectomy with bilateral or unilateral salpingo-oophorectomy specimens were examined for mean number of CICs and their epithelial type between two groups of the patients. Group A included the patients who were on oral contraceptive pills for more than 5 years. All of the subjects with other contraceptive methods or a history of less than 5 years contraceptive pills usage were stratified in group B. Sections from 20 cases in which more than five inclusion cysts were found, were selected for IHC staining with calretinine and PAX8 as markers for mesothelium and mullerian epithelium respectively.
  
  
  RESULTS
  The mean age of the patients was 51.67 years with no significant differences between two groups. The mean number of cysts were 1.27 and 3.23 in group A and B respectively (P =0.0001). Similarly the mean number of CICs, lined by tubal epithelium, was significantly different between two groups (0.65 vs 2.65, P =0.0001). In IHC staining 123 out of 150 CICs (82 %) were PAX+ while only 7 CICs (4.8 %) showed positive reaction for calretinin irrespective of type of epithelium.
  
  
  CONCLUSIONS
  Our findings showed that the use of OCP for more than five years in women, significantly prevents development of cortical inclusion cysts in the ovaries which lined by tubal (PAX8 positive) type epithelium. These findings may explain the alternative mechanism of oral contraceptive pills or long time use of progesterone in suppression of tubal type overgrowth and subsequently prevention of ovarian epithelial cancers.
authors.affiliation: Women's Reproductive Health Research Center, Tabriz University of Medical Sciences-Iran, Tabriz, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: DastranjTabrizi
authors.affiliation: Women's Reproductive Health Research Center, Tabriz University of Medical Sciences-Iran, Tabriz, Iran.
authors.forename: Parvin
authors.initials: P
authors.lastname: MostafaGharabaghi
authors.affiliation: Department of Physiology, Faculty of Science, Tabriz University-Iran, Tabriz, Iran. drhesari@gmail.com.
authors.forename: Farzam
authors.initials: F
authors.lastname: SheikhzadehHesari
authors.affiliation: Women's Reproductive Health Research Center, Tabriz University of Medical Sciences-Iran, Tabriz, Iran.
authors.forename: Liela
authors.initials: L
authors.lastname: Sadeghi
authors.affiliation: Department of Physiology, Faculty of Science, Tabriz University-Iran, Tabriz, Iran.
authors.forename: Sharareh
authors.initials: S
authors.lastname: Zamanvandi
authors.affiliation: Department of Statistic and Epidemiology, Faculty of Nutrition and Health, Tabriz University of Medical Sciences-Iran, Tabriz, Iran.
authors.forename: Parvin
authors.initials: P
authors.lastname: Sarbakhsh
authors.affiliation: Women's Reproductive Health Research Center, Tabriz University of Medical Sciences-Iran, Tabriz, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Ghojazadeh
mesh_terms: D000328:Adult; D000368:Aged; D064032:Calbindin 2 / Q000032:analysis; D000077216:Carcinoma, Ovarian Epithelial; D060833:Cellular Microenvironment; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005187:Fallopian Tubes / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008679:Metaplasia; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000473:pathology / Q000517:prevention & control; D010048:Ovarian Cysts / Q000737:chemistry / Q000473:pathology / Q000517:prevention & control*; D010051:Ovarian Neoplasms / Q000473:pathology / Q000517:prevention & control; D010053:Ovary / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000032:analysis; D010641:Phenotype
chemical_list: C576764:CALB2 protein, human; D064032:Calbindin 2; D003278:Contraceptives, Oral, Hormonal; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors
keywords: Oral contraceptive pills; Ovarian cancer; Ovarian cortical inclusion cyst