title: Expression of the mammalian target of rapamycin pathway markers in lung adenocarcinoma and squamous cell carcinoma.
abstract: OBJECTIVE
  We investigated whether the expression of mammalian target of rapamycin (mTOR) pathway components is associated with clinicopathologic characteristics and patient outcome in lung adenocarcinoma (AC) and squamous cell carcinoma (SCC).
  
  
  METHODS
  We used immunohistochemistry to evaluate the expression of phosphorylated Akt (pAkt), mTOR, p70 ribosomal protein S6 kinase (p70S6K) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in 91 cases of AC and 154 cases of SCC.
  
  
  RESULTS
  pAkt expression was positively correlated with the expression of mTOR (p < 0.001) and p70S6K (p < 0.001), and mTOR expression was positively correlated with p70S6K expression (p < 0.001). PTEN expression was inversely correlated with the expression of pAkt (p = 0.001), mTOR (p < 0.001) and p70S6K (p = 0.012). In addition, loss of PTEN expression, observed in 37.4% (34/91) of AC patients, was significantly associated with a higher histologic grade (p = 0.013), pathologic T stage (p = 0.016) and N stage (p < 0.001) and advanced TNM stage (p = 0.001), as well as a shorter overall survival of AC patients (p = 0.015).
  
  
  CONCLUSIONS
  The high prevalence of PTEN loss and its association with aggressive tumor behavior and poor patient outcome in AC suggest that loss of PTEN expression is involved in AC progression and serves as a prognostic marker for patients with AC.
authors.affiliation: Department of Pathology, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Sung-Jig
authors.initials: SJ
authors.lastname: Lim
authors.forename: Youn Wha
authors.initials: YW
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human