title: Potential scenarios leading to ovarian cancer arising from endometriosis.
abstract: OBJECTIVE
  The aim of this review was to highlight recent advances in our understanding of the pathogenesis of malignant transformation of endometriosis.
  
  
  METHODS
  This study reviewed the English-language literature concerning basic science studies of the potential promotion of carcinogenesis.
  
  
  RESULTS
  Repeated episodes of hemorrhage occur in endometriosis at the onset of menstruation. Extracellular hemoglobin, heme, and iron derivatives in endometriosis cause DNA damage and mutations, which create increased cellular susceptibility to oxidant-mediated cell killing. Excess DNA damage and mutations are linked to cell death, but not carcinogenesis. In response to an oxidative and inflammatory microenvironment, endometriotic cells and macrophages secrete antioxidants that control excess oxidative stress in the surrounding environment. Exposure of endometriotic cells to a sublethal level of oxidative stress may lead to carcinogenesis. Macrophages also secrete immunosuppressive factors that lead to promotion of malignant transformation.
  
  
  CONCLUSIONS
  At least two potential scenarios could result in ovarian cancer arising from endometriosis. The first step: extracellular hemoglobin, heme, and iron cause cellular oxidative damage by promoting reactive oxygen species formation, which results in DNA damage and mutations (ovarian cancer initiation from endometriosis). The second step: cancer progression may be associated with persistent antioxidant production favoring a protumoral microenvironment.
authors: a Department of Obstetrics and Gynecology , Nara Medical University , Japan.
authors: Hiroshi
authors: H
authors: Kobayashi
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004249:DNA Damage / Q000235:genetics; D004715:Endometriosis / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D007501:Iron
keywords: Antioxidants; Carcinogenesis; Endometriosis; Oxidative stress