title: Activation of mTOR signaling pathway associated with adverse prognostic factors of epithelial ovarian cancer.
abstract: OBJECTIVE
  Activation of the mammalian target of rapamycin (mTOR) pathway enhances cell survival and growth by regulating the efficiency of protein translation. This study was conducted to evaluate the association of activated mTOR signaling molecules with the clinicopathologic characteristics in epithelial ovarian cancer.
  
  
  METHODS
  Immunohistochemical staining with antibodies against p-4EBP1, p-mTOR, and p-p70S6K were performed on specimens of 103 patients with ovarian cancer. Tumors were classified as chemoresistant in cases where time to recurrence after the end of chemotherapy was shorter than 6months.
  
  
  RESULTS
  Expressions of p-mTOR, p-4EBP1, and p-p70S6K were detected in 47.6%, 85.4%, and 64.1% of all patients, respectively. p-4EBP1 overexpression was associated with advanced stage (p=0.04), histologic grade (p<0.01), residual mass (p<0.01), shorter disease-free survival rate (p=0.01) and chemoresistance (p=0.02). p-p70S6K was associated with residual mass with marginal significance (p=0.06). p-4EBP1 expression was correlated with p-p70S6K expression (r=0.42, p<0.01), whereas p-mTOR was not associated with expression of its downstream effectors or prognostic factors.
  
  
  CONCLUSIONS
  Our findings suggest that p-4EBP1 expression was associated with poor prognostic factors of ovarian cancer and that p-4EBP1 overexpression may be a prognostic biomarker of ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: No
authors.forename: Yong-Tark
authors.initials: YT
authors.lastname: Jeon
authors.forename: In-Ae
authors.initials: IA
authors.lastname: Park
authors.forename: Yong-Beom
authors.initials: YB
authors.lastname: Kim
authors.forename: Jae Weon
authors.initials: JW
authors.lastname: Kim
authors.forename: Noh-Hyun
authors.initials: NH
authors.lastname: Park
authors.forename: Soon-Beom
authors.initials: SB
authors.lastname: Kang
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Han
authors.forename: Jeong Mook
authors.initials: JM
authors.lastname: Lim
authors.forename: Yong-Sang
authors.initials: YS
authors.lastname: Song
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000077216:Carcinoma, Ovarian Epithelial; D018797:Cell Cycle Proteins; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011379:Prognosis; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases