title: Tumor p16M is a possible marker of advanced stage in non-small cell lung cancer.
abstract: OBJECTIVE
  The inactivation of the tumor suppressor gene p16 by methylation (p16M) has been recognized recently as an important process in the oncogenesis for a variety of carcinomas. There have been few reports of its use in lung cancer. We investigate p16M in patients with non-small cell lung cancer (NSCLC).
  
  
  METHODS
  p16M in tumor, plasma, and pleural lavage fluid from patients with resectable NSCLC were investigated by using methylation-specific polymerase chain reaction.
  
  
  RESULTS
  Of the 33 patients studied, 14 (42%) had p16M tumors. There was a significant association between p16M tumors and advanced TNM staging (stage III or IV, P=0.047, Fisher exact test). Circulating p16M was identified in 2 of the 14 patients with p16M tumor and was also associated with advanced TNM staging (P=0.049). The presence of plasma p16M in NSCLC patients and in p16M tumor patients was associated with poor survival and shorter disease-free survival (P=0.0028, P=0.0039, Kaplan-Meier log rank). In addition, p16M was present in three preresectional and four postresectional lavage samples. Preresectional p16M was associated with poor survival and shorter disease-free survival (P=0.0085). p16M tumor involving the visceral pleura was significantly associated with positive p16M postresectional lavage.
  
  
  CONCLUSIONS
  Positive tumor and plasma p16M indicate advanced staging in NSCLC. Patients with plasma and preresection pleural lavage p16M have shorter survival. Further research in this direction is warranted.
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shantin, NT, Hong Kong.
authors.forename: Calvin S H
authors.initials: CS
authors.lastname: Ng
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Song
authors.initials: S
authors.lastname: Wan
authors.forename: Tak Wai
authors.initials: TW
authors.lastname: Lee
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Arifi
authors.forename: Tony
authors.initials: T
authors.lastname: Mok
authors.forename: Dennis Y M
authors.initials: DY
authors.lastname: Lo
authors.forename: Anthony P C
authors.initials: AP
authors.lastname: Yim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology* / Q000601:surgery; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D019942:Genes, p16; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000601:surgery; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D011013:Pneumonectomy; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm