title: Combined loss of PTEN and p27 expression is associated with tumor cell proliferation by Ki-67 and increased risk of recurrent disease in localized prostate cancer.
abstract: OBJECTIVE
  Recent experimental work indicates a major role for PTEN and p27 in prostate cancer. The combined loss of PTEN and p27 was found to strongly increase the development of prostatic carcinomas in an animal model, and a prognostic value in human tumors was postulated. The purpose of our study was to examine the impact of PTEN and p27 on prognosis in a series of prostate cancer patients, using high-density tissue microarray technology for expression profile analysis of PTEN, p27, and tumor cell proliferation.
  
  
  METHODS
  The expression of PTEN and p27 was examined in primary prostatic carcinomas from 104 patients treated with radical prostatectomy and with complete follow-up available. Using high-throughput tissue microarrays, the expression of PTEN and p27 was examined by immunohistochemistry, and the results were related to clinicopathological variables, tumor cell proliferation (Ki-67), and time to disease progression.
  
  
  RESULTS
  PTEN was negative in 28 of 103 tumors (27.2%), and median p27 expression was 64%. Combined loss of PTEN and p27 expression defined a group of 18 tumors (17.5%) associated with increased tumor diameter, seminal vesicle invasion, increased pathological stage, and elevated tumor cell proliferation by Ki-67. Cox regression analysis revealed that loss of PTEN/p27 expression and histological grade were both independent predictors of time to biochemical failure and clinical recurrence.
  
  
  CONCLUSIONS
  Our findings strongly support the importance of PTEN and p27 for the progression of human prostate cancer because loss of PTEN/p27 expression was associated with adverse pathological parameters, tumor cell proliferation, and increased risk of recurrence.
authors.affiliation: Department of Pathology, The Gade Institute, Haukeland University Hospital, N-5021 Bergen, Norway.
authors.forename: Ole J
authors.initials: OJ
authors.lastname: Halvorsen
authors.forename: Svein A
authors.initials: SA
authors.lastname: Haukaas
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
mesh_terms: D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D002455:Cell Division; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008297:Male; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D012008:Recurrence; D012306:Risk; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
chemical_list: D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human