Loss of phosphatase and tensin homologue deleted on chromosome 10 and phosphorylation of mammalian target of rapamycin are associated with progesterone refractory endometrial hyperplasia

International Journal of Gynecological Cancer

Volumn 18, Issue 1, 2008, Pages 146-151

  Milam, M R ^a   Soliman, P T ^a   Chung, L H ^a   Schmeler, K M ^a   Bassett Jr , R L ^a   Broaddus, R R ^a   Lu, K H ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

Endometrial hyperplasia; mTOR; Progesterone; PTEN

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN; MEDROXYPROGESTERONE; MEGESTROL; NORETHISTERONE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROGESTERONE; PROTEIN P27;

ADULT; AGED; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; ENDOMETRIUM BIOPSY; ENDOMETRIUM HYPERPLASIA; FEMALE; HORMONAL THERAPY; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION;

ADULT; AGED; CHROMOSOMES, HUMAN, PAIR 10; CYCLIN-DEPENDENT KINASE INHIBITOR P27; ENDOMETRIAL HYPERPLASIA; FEMALE; GENE DELETION; HUMANS; IMMUNOENZYME TECHNIQUES; MIDDLE AGED; NEOPLASM RECURRENCE, LOCAL; PHOSPHORYLATION; PROGESTERONE; PROGESTINS; PROTEIN KINASES; PTEN PHOSPHOHYDROLASE;

EID: 38049085766     PISSN: 1048891X     EISSN: 15251438     Source Type: Journal    
DOI: 10.1111/j.1525-1438.2007.00958.x     Document Type: Article

References (19)

1. Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long-term study of "untreated" hyperplasia in 170 patients. Cancer 1985 56 : 403 12.
2. ACOG practice bulletin, clinical management guidelines for obstetrician-gynecologists, number 65, August 2005: management of endometrial cancer. Obstet Gynecol 2005 : 106 : 413 25.
3. Granville CA, Memmott RM, Gills JJ et al. Handicapping the race to develop inhibitors of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway. Clin Cancer Res 2006 12 : 679 89.
4. Maxwell GL, Risinger JI, Tong B et al. Mutation of the PTEN tumor suppressor gene is not a feature of ovarian cancers. Gynecol Oncol 1998 70 : 13 6.
5. Mutter GL, Lin MC, Fitzgerald JT et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 2000 92 : 924 30.
6. Risinger JI, Hayes AK, Berchuck A et al. PTEN/MMAC1 mutations in endometrial cancers. Cancer Res 1997 57 : 4736 8.
7. Guertin DA, Sabatini DM. An expanding role for mTOR in cancer. Trends Mol Med 2005 11 : 353 61.
8. An HJ, Lee YH, Cho NH et al. Alteration of PTEN expression in endometrial carcinoma is associated with down-regulation of cyclin-dependent kinase inhibitor, p27. Histopathology 2002 41 : 437 45.
9. Erkanli S, Kayaselcuk F, Kuscu E et al. Expression of survivin, PTEN and p27 in normal, hyperplastic, and carcinomatous endometrium. Int J Gynecol Cancer 2006 16 : 1412 8.
10. Zheng W, Baker HE, Mutter GL. Involution of PTEN-null endometrial glands with progestin therapy. Gynecol Oncol 2004 92 : 1008 13.
11. Slomovitz BM, Broaddus RR, Soliman PT et al. mTOR inhibition is a rational target for the treatment of endometrial cancer. 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition) 2004 22 : 5076.
12. Amezcua CA, Lu JJ, Felix JC et al. Apoptosis may be an early event of progestin therapy for endometrial hyperplasia. Gynecol Oncol 2000 79 : 169 76.
13. Ferenczy A, Gelfand M. The biologic significance of cytologic atypia in progestogen-treated endometrial hyperplasia. Am J Obstet Gynecol 1989 160 : 126 31.
14. Randall TC, Kurman RJ. Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of the endometrium in women under age 40. Obstet Gynecol 1997 90 : 434 40.
15. Horn LC, Schnurrbusch U, Bilek K et al. Risk of progression in complex and atypical endometrial hyperplasia: clinicopathologic analysis in cases with and without progestogen treatment. Int J Gynecol Cancer 2004 14 : 348 53.
16. Wang S, Pudney J, Song J et al. Mechanisms involved in the evolution of progestin resistance in human endometrial hyperplasia - precursor of endometrial cancer. Gynecol Oncol 2003 88 : 108 17.
17. Yamashita H, Otsuki Y, Matsumoto K et al. Fas ligand, Fas antigen and Bcl-2 expression in human endometrium during the menstrual cycle. Mol Hum Reprod 1999 5 : 358 64.
18. Podsypanina K, Lee RT, Politis C et al. An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice. Proc Natl Acad Sci U S A 2001 98 : 10320 5.
19. Milam MR, Wu W, Broaddus RR et al. Reduced progression of endometrial hyperplasia with oral mTOR inhibition in the Pten heterozygote murine model. Am J Obstet Gynecol 2007 196 (3 247, e1-5.