Involution of PTEN-null endometrial glands with progestin therapy.
OBJECTIVE
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.
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
Wenxin
W
Zheng
Heather E
HE
Baker
George L
GL
Mutter
D000328:Adult; D000368:Aged; D004714:Endometrial Hyperplasia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008875:Middle Aged; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency* / Q000235:genetics; D011372:Progestins / Q000627:therapeutic use*; D025521:Tumor Suppressor Proteins / Q000172:deficiency* / Q000235:genetics
D011372:Progestins; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human