PMID- 17466036
OWN - NLM
STAT- MEDLINE
DCOM- 20080325
LR  - 20211203
IS  - 1525-1438 (Electronic)
IS  - 1048-891X (Linking)
VI  - 18
IP  - 1
DP  - 2008 Jan-Feb
TI  - Loss of phosphatase and tensin homologue deleted on chromosome 10 and 
      phosphorylation of mammalian target of rapamycin are associated with progesterone 
      refractory endometrial hyperplasia.
PG  - 146-51
AB  - 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.
FAU - Milam, M R
AU  - Milam MR
AD  - Department of Gynecologic Oncology, University of Texas MD Anderson Cancer 
      Center, Houston, Texas, USA.
FAU - Soliman, P T
AU  - Soliman PT
FAU - Chung, L H
AU  - Chung LH
FAU - Schmeler, K M
AU  - Schmeler KM
FAU - Bassett, R L Jr
AU  - Bassett RL Jr
FAU - Broaddus, R R
AU  - Broaddus RR
FAU - Lu, K H
AU  - Lu KH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070426
PL  - England
TA  - Int J Gynecol Cancer
JT  - International journal of gynecological cancer : official journal of the 
      International Gynecological Cancer Society
JID - 9111626
RN  - 0 (Progestins)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Chromosomes, Human, Pair 10/*genetics
MH  - Cyclin-Dependent Kinase Inhibitor p27/*metabolism
MH  - Endometrial Hyperplasia/*drug therapy/genetics/pathology
MH  - Female
MH  - *Gene Deletion
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/drug therapy/metabolism/pathology
MH  - PTEN Phosphohydrolase/*genetics
MH  - Phosphorylation/drug effects
MH  - Progesterone/*therapeutic use
MH  - Progestins/*therapeutic use
MH  - Protein Kinases/*metabolism
MH  - TOR Serine-Threonine Kinases
EDAT- 2007/05/01 09:00
MHDA- 2008/03/26 09:00
CRDT- 2007/05/01 09:00
PHST- 2007/05/01 09:00 [pubmed]
PHST- 2008/03/26 09:00 [medline]
PHST- 2007/05/01 09:00 [entrez]
AID - IJG958 [pii]
AID - 10.1111/j.1525-1438.2007.00958.x [doi]
PST - ppublish
SO  - Int J Gynecol Cancer. 2008 Jan-Feb;18(1):146-51. doi: 
      10.1111/j.1525-1438.2007.00958.x. Epub 2007 Apr 26.