title: Ectopic pregnancy: histopathology and assessment of cell proliferation with and without methotrexate treatment.
abstract: OBJECTIVE
  To evaluate tubal morphology, trophoblast proliferation, and inflammatory reaction in response to methotrexate (MTX) treatment of ectopic pregnancy (EP).
  
  
  METHODS
  Nonrandomized controlled study.
  
  
  METHODS
  Academic hospital.
  
  
  METHODS
  Archival specimens from 10 EP unsuccessfully treated with MTX and 10 cases primarily treated by surgery.
  
  
  METHODS
  Ki67/hCG and Ki67/human placental lactogen double immunohistochemical methods were used to examine trophoblastic spread, placentation, hormone production, decidualization, vascular invasion, hemorrhage, rupture, and proliferative index of the cytotrophoblast. B and T-lymphocyte responses were evaluated by CD3 and CD20.
  
  
  RESULTS
  Trophoblastic spread and placentation were confined to the tubal mucosa after MTX treatment, whereas invasion of the muscularis and subserosa was common in the controls. The proliferative index was reduced (19 percent versus 93 percent), although a high proliferative index was found in two of three cases complicated by rupture. Polar proliferation of Ki67-positive cytotrophoblast toward the implantation site was abolished in MTX-treated cases. Decidual reaction was not observed. No correlation was observed between the above-mentioned findings and gestational age, level of beta-hCG, dose of MTX, or interval to surgery.
  
  
  CONCLUSIONS
  Trophoblastic spread, differentiation, and invasion were compromised by MTX treatment. Methotrexate seems to decrease cytotrophoblast proliferation. Whether a missing decrease in proliferation index reflects treatment failure awaits a larger population-based study.
authors.forename: C
authors.initials: C
authors.lastname: Floridon
authors.forename: O
authors.initials: O
authors.lastname: Nielsen
authors.forename: C
authors.initials: C
authors.lastname: Byrjalsen
authors.forename: B
authors.initials: B
authors.lastname: Hølund
authors.forename: G
authors.initials: G
authors.lastname: Kerndrup
authors.forename: S G
authors.initials: SG
authors.lastname: Thomsen
authors.forename: J A
authors.initials: JA
authors.lastname: Andersen
mesh_terms: D002455:Cell Division / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000378:metabolism; D005260:Female; D005493:Folic Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D008727:Methotrexate / Q000627:therapeutic use*; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010928:Placental Lactogen / Q000378:metabolism; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D006063:Chorionic Gonadotropin; D005493:Folic Acid Antagonists; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010928:Placental Lactogen; D008727:Methotrexate