Tumor p16M is a possible marker of advanced stage in non–small cell lung cancer

Abstract

Background and Objectives 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. J. Surg. Oncol. 2002;79:101–106.