title: Prognostic value of the immunohistochemical detection of p16INK4 expression in nonsmall cell lung carcinoma.
abstract: BACKGROUND
  The product of the p16INK4/CDKN2/MTS1 (p16) controls the transition from the G1 phase to the S-phase in the cell cycle by inhibiting the phosphorylation of the retinoblastoma gene product. A lack of p16 expression has been reported in various cancer cell lines and tumors; however, there have been only a few reports on the prognostic significance of p16 alteration. The authors studied p16 expression in nonsmall cell lung carcinoma (NSCLC) and also examined its correlation with clinicopathologic features and prognosis.
  
  
  METHODS
  p16 expression was determined by immunohistochemical analysis of 115 paraffin specimens of primary NSCLC that were curatively resected. The immunohistochemical study was performed using the labeled streptavidin-biotin method with anti-p16 rabbit polyclonal antibody.
  
  
  RESULTS
  Thirty-one of 115 NSCLC specimens (27%) showed negative p16 staining. The frequency of negative p16 expression was significantly higher in squamous cell carcinoma (39.5%) than in adenocarcinoma (20.3%) (P = 0.026). There were no statistically significant differences in the p16 status with respect to age, gender, smoking history, histologic differentiation, or stage of the disease. The Kaplan-Meier survival curves demonstrated that patients with negative p16 expression survived for a significantly shorter period of time than those with positive p16 expression (P = 0.043). p16 status was a significant prognostic factor, especially in patients with early stage disease (Stages I-II) (P = 0.039).
  
  
  CONCLUSIONS
  A lack of p16INK4 expression in NSCLC was observed more frequently in squamous cell carcinoma than in adenocarcinoma, and also was found to be closely related to prognosis, especially in patients with early stage squamous cell carcinoma.
authors.affiliation: Department of Surgery II, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Taga
authors.forename: T
authors.initials: T
authors.lastname: Osaki
authors.forename: A
authors.initials: A
authors.lastname: Ohgami
authors.forename: H
authors.initials: H
authors.lastname: Imoto
authors.forename: T
authors.initials: T
authors.lastname: Yoshimatsu
authors.forename: I
authors.initials: I
authors.lastname: Yoshino
authors.forename: K
authors.initials: K
authors.lastname: Yano
authors.forename: R
authors.initials: R
authors.lastname: Nakanishi
authors.forename: Y
authors.initials: Y
authors.lastname: Ichiyoshi
authors.forename: K
authors.initials: K
authors.lastname: Yasumoto
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000368:Aged; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins