title: Loss of phosphatase and tensin homolog protein expression is an independent poor prognostic marker in lung adenocarcinoma.
abstract: BACKGROUND
  Phosphatase and tensin homolog (PTEN) has been established as a tumor suppressor gene with an important role in regulating the phosphatidylinositol-3-kinase/AKT antiapoptotic and survival pathway. The prognostic role of PTEN in non-small-cell lung carcinoma has not been evaluated completely in the context of other molecular information.
  
  
  METHODS
  Tissue microarrays containing 152 resected non-small-cell lung cancer specimens were used to investigate PTEN and p53 by immunohistochemistry and PTEN by fluorescence in situ hybridization. DNA was isolated and subjected to mutational profiling using the Sequenom Oncocarta v1.0 panel. Clinicopathological features were correlated with PTEN expression, gene copy number, and mutation status.
  
  
  RESULTS
  PTEN staining was absent in 63 (41.4%) of the cases. Significantly more squamous cell carcinomas compared with adenocarcinomas demonstrated loss of (negative) PTEN staining (26 of 44 [59%] versus 32 of 94 [34%]; p = 0.009). PTEN gene copy deletion was present in only seven of 124 evaluable cases (5.6%); all deleted cases were immunohistochemistry negative. In univariate and multivariate (MV) analyses adjusted for sex, age, histology, and stage, loss of PTEN protein expression was associated with significantly shorter disease-free survival (MV hazard ratio: 1.78, 95% confidence interval: 1.01-3.14, p = 0.048), whereas no significant associations were seen with p53 or KRAS and epidermal growth factor receptor (EGFR) mutation status. Importantly, the prognostic value of absent PTEN staining was limited to adenocarcinomas, with MV disease-free survival hazard ratio of 2.68 (95% confidence interval: 1.35-5.32, p = 0.005), whereas no such association was seen in squamous cell carcinomas.
  
  
  CONCLUSIONS
  Absence of PTEN protein expression is an independent prognostic marker in early-stage resected lung adenocarcinoma.
authors.affiliation: Department of Pathology and Laboratory Medicine, Yamagata Prefectural Central Hospital, Yamagata, Yamagata, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yanagawa
authors.forename: Charles
authors.initials: C
authors.lastname: Leduc
authors.forename: Derek
authors.initials: D
authors.lastname: Kohler
authors.forename: Mauro A
authors.initials: MA
authors.lastname: Saieg
authors.forename: Thomas
authors.initials: T
authors.lastname: John
authors.forename: Jenna
authors.initials: J
authors.lastname: Sykes
authors.forename: Maisa
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.forename: Jeremy
authors.initials: J
authors.lastname: Squire
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D018628:Gene Dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C512478:EGFR protein, human; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins