title: Loss of phosphatase and tensin homologue deleted on chromosome 10 and phosphorylation of mammalian target of rapamycin are associated with progesterone refractory endometrial hyperplasia.
abstract: The objective of our study was to evaluate the phosphatase and tensin homologue deleted on chromosome 10 (PTEN), p27, and mammalian target of rapamycin (mTOR) expressions in women with progesterone-responsive and refractory endometrial hyperplasia (EH) samples and to determine if these markers could be associated with response or used as potential targets for treatment. Thirty-eight matched pre- and posttreatment pairs of paraffin-embedded endometrial biopsies were obtained from patients with EH. Immunohistochemical analysis for PTEN, p27, and phospho-mTOR were performed on all samples. Median age at diagnosis was 49 years (20-79 years). Median treatment interval was 3 months (1-12 months). Sixteen patients (42.1%) had complete resolution of their hyperplasia (responders), and 22 (57.9%) had persistent hyperplasia (nonresponders) after treatment with progesterone. In the pretreatment samples, no markers were found to predict nonresponders. In posttreatment samples, loss of PTEN expression with phospho-mTOR expression was observed in more nonresponders than responders (40.9% vs 6.3%; P= 0.03). Phospho-mTOR overexpression was found in 63.6% of nonresponders. We found that persistent hyperplasia refractory to progesterone therapy was associated both with the loss of PTEN and with the loss of phosphorylation of mTOR. In select cases of non-responsive progesterone refractory EH, a rational target for treatment may involve the mTOR pathway.
authors.affiliation: Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Milam
authors.forename: P T
authors.initials: PT
authors.lastname: Soliman
authors.forename: L H
authors.initials: LH
authors.lastname: Chung
authors.forename: K M
authors.initials: KM
authors.lastname: Schmeler
authors.forename: R L
authors.initials: RL
authors.lastname: Bassett
authors.forename: R R
authors.initials: RR
authors.lastname: Broaddus
authors.forename: K H
authors.initials: KH
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D004714:Endometrial Hyperplasia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D011374:Progesterone / Q000627:therapeutic use*; D011372:Progestins / Q000627:therapeutic use*; D011494:Protein Kinases / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases
chemical_list: D011372:Progestins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D011374:Progesterone; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human