title: Activation of mammalian target of rapamycin signaling pathway markers in minute adenocarcinoma of the prostate.
abstract: OBJECTIVE
  To asses the mammalian target of rapamycin (mTOR) pathway in minute prostatic adenocarcinoma on the basis of the previously reported role of phosphatase and tensin homolog (PTEN) inactivation and mTOR pathway activation as a negative prognosticator in prostatic cancer.
  
  
  METHODS
  Tissue microarrays were constructed from 42 consecutive radical prostatectomy specimens with minute prostatic adenocarcinoma. Standard immunohistochemistry analysis for mTOR pathway members PTEN, phos-S6, phos-4E-BP1, phos-mTOR, phos-AKT, p27, and ERG was performed. For all markers, histologic expression score was calculated as the sum of intensity × extent of expression. In addition, for PTEN, presence of "markedly decreased" expression (any focal absence of expression) was also assessed. Expression status of all biomarkers was compared between tumor and paired benign tissue. Intercorrelation among markers was also performed.
  
  
  RESULTS
  PTEN expression was seen in all 36 evaluable minute prostatic adenocarcinoma. Cytoplasmic phos-S6 was present in 32 of 36 tumors (89%). phos-S6 expression levels were higher in tumors compared with paired benign tissue (P = .007). Cytoplasmic and nuclear phos-4E-BP1 was present in all 34 evaluable tumors. phos-4E-BP1 was significantly higher in cancer compared with normal tissue (P <.0001). Only a minority of tumors demonstrating higher phos-S6 expression and phos-4E-BP1 (2 of 32 and 2 of 34, respectively) had associated "markedly decreased" PTEN expression.
  
  
  CONCLUSIONS
  We found evidence of activation of mTOR pathway in minute prostatic adenocarcinoma that appears to be unrelated to "markedly decreased" PTEN expression. The latter finding suggests an alternative signaling mechanism controlling mTOR activation in minute prostate carcinoma.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.
authors.forename: Sheila F
authors.initials: SF
authors.lastname: Faraj
authors.forename: Roula
authors.initials: R
authors.lastname: Albadine
authors.forename: Alcides
authors.initials: A
authors.lastname: Chaux
authors.forename: Nilda
authors.initials: N
authors.lastname: Gonzalez-Roibon
authors.forename: Jessica
authors.initials: J
authors.lastname: Hicks
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Humphreys
authors.forename: Alan
authors.initials: A
authors.lastname: Partin
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015331:Cohort Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human