Predictive survival markers in patients with surgically resected non-smallcell lung carcinoma

Among patients with resected non-small cell lung carcinoma, about 50% will present a tumor recurrence. Thus, it would be of major importance to be abl e to predict and try to prevent these relapses by an active chemotherapy an d/or radiotherapy. In an attempt to answer this question, the tumors of 227 patients with a su rgically resected non-small cell lung carcinoma were evaluated as follows: tumors were classified as squamous cell carcinoma (n = 132) or adenocarcino ma (n = 95), and tumor differentiation was evaluated for each type, Then, a ll tumors were classified in respect to their pathological TNM staging (WHO ) and screened by immunohistochemistry for the detection of the expression of the following antigens: Bcl-2, A+B+H blood group antigens, c-erb-b2, p53 , and Pan-Ras antigens, Furthermore, adenocarcinomas were screened for the presence of point mutations in Ki-Ras codons 1-31. Finally, the patient blo od group was defined, and patient survival was analyzed using nonparametric tests and proportional hazard Cox models. Using Kaplan-Meier survival curves, disease pathological TNM staging was sh own to be a strong predictive factor of survival for both squamous cell car cinoma and adenocarcinoma, Patients with squamous cell carcinoma experience d fewer relapses than those with adenocarcinoma (42% versus 63%; P = 0.0002 ) and had a significantly better survival. All evaluated antigens were more often present in squamous cell carcinoma t han in adenocarcinoma except for Pan-Ras (three times more frequent in aden ocarcinoma). In patients with squamous cell carcinoma, only tumor staging had a signific ant prognosis value (P = 0.01). In patients with lung adenocarcinoma, a well-differentiated tumor (P = 0.00 9) as well as a positive Bcl-2 staining (P = 0.009) and an A+B+H antigen tu mor staining (P = 0.024) were associated with a better survival, In contras t, patients with a stage I or IT disease and a p53-positive tumor staining and patients,vith the O blood group (P = 0.01) had a shorter survival. Inte restingly, no relation with patient survival was related to c-erb-b2 and Pa n-Ras staining. Finally, 12 point mutations were found out of 81 tumors (15 %) evaluated for Ki-Ras codons 1-31; they involved codon 12 but also 8, 14 , and 15 without any relationship to survival. In respect to lung adenocarcinoma, using Cox proportional hazard models str atified on tumor staging, the following markers were shown to be related to survival: (a) Independent markers of longer survival (i.e., high histologi cal degree of tumor differentiation and positive Bcl-2 and A+B+H blood grou p antigen expression by tumor cells); and (b) Independent markers of shorte r survival (i.e., O blood group for all patients and p53 tumor staining in patients with stage I and II diseases), This study suggests that, in patients who undergo surgery for lung adenocar cinoma, the presence or absence of these criteria could be used to define a subset of patients who may benefit from a more specific follow-up.