Involution of PTEN-null endometrial glands with progestin therapy

Gynecol Oncol. 2004 Mar;92(3):1008-13. doi: 10.1016/j.ygyno.2003.11.026.


Objectives: Loss of PTEN tumor suppressor gene function characterizes most (63%) endometrial precancerous lesions (endometrial intraepithelial neoplasia, EIN) and up to 83% of endometrioid endometrial cancers. Because systemic progestins are known to promote involution of precancerous endometrial lesions, we tested the hypothesis that this therapy preferentially leads to clearance of immunohistochemically detected PTEN-null endometrial glands in a variety of histopathologic settings.

Methods: PTEN immunohistochemistry of pre and postprogestin-treated endometria was successfully performed on 17 women presenting with an intake endometrial biopsy diagnosis of "hyperplasia". Intake biopsies were rediagnosed using EIN criteria as 5 normal (proliferative or secretory), 4 anovulatory, 3 polyps, and 5 EIN endometria. The persistence of PTEN-null glands in progestin-treated patients was compared to that seen previously in rebiopsied normal proliferative endometrium of endogenously cycling premenopausal women.

Results: Ten of 17 women prehormonal therapy had PTEN-null glands in the initial biopsy, and 90% (9/10) of these disappeared in the postprogestin sample. This contrasts with only 17% (2/12) involution in the endometria of normal cycling women (Fishers exact test P=0.002, Odds Ratio 45).

Conclusions: We conclude that progestin therapy promotes involution, or disappearance, of PTEN-null endometrial glands relative to the persistence rate seen for normal cycling women. This effect occurs among PTEN-null glands having a variety of histopathologic presentations.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Endometrial Hyperplasia / drug therapy*
  • Endometrial Hyperplasia / genetics
  • Endometrial Hyperplasia / metabolism*
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Middle Aged
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / deficiency*
  • Phosphoric Monoester Hydrolases / genetics
  • Progestins / therapeutic use*
  • Tumor Suppressor Proteins / deficiency*
  • Tumor Suppressor Proteins / genetics


  • Progestins
  • Tumor Suppressor Proteins
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human