Prognostic markers in resectable non-small cell lung cancer: a multivariate analysis.
OBJECTIVE
To identify the prognostic significance of certain clinical, cellular and immunologic markers in resectable non-small cell lung cancer (NSCLC).


METHODS
A cohort of patients with resectable NSCLC was prospectively followed up for 8 years (100% follow-up).


METHODS
A university hospital in a large Canadian city.


METHODS
One hundred and thirteen consecutive patients who underwent surgical resection of primary NSCLC.


METHODS
Presence of peritumoral B lymphocytes (identified with antibody to CD20) and T lymphocytes (antibody to CD43), along with tumour markers (carcinoembryonic antigen [CEA], keratin, cytokeratin, S-100 protein, vimentin, chromogranin) and other factors such as age, sex, cell type, American Joint Committee on Cancer (AJCC) stage, histologic grade, DNA ploidy and S-phase fraction were correlated with survival.


RESULTS
The mean age of patients in the study was 66.0 years; 60% were male. Histologic types of the tumours were: adenocarcinoma 57 (50.4%), squamous cell 47 (41.6%), adenosquamous 6 (5.3%) and large cell 3 (2.6%). AJCC stages were: I 66 (58.4%), II 20 (17.7%) and III 27 (23.9%). Histologic grades were: I (well differentiated) 31 (27.4%), II 50 (44.2%), III 29 (25.7%) and IV 3 (2.6%). Survival was 85% at 1 year (95% confidence interval [CI] 76%-90%), 44% at 5 years (95% CI 34%-53%) and 34% at 10 years (95% CI 22%-46%). Multivariate analyses using the Cox proportional hazards model for survival confirmed AJCC stage (p < 0.001) in all histologic subtypes to be the strongest factor of independent prognostic significance. It also revealed the presence of CD20-stained B lymphocytes (p = 0.04) in the peritumoral region of all tumours to be a positive prognostic factor. This relation was especially strong for nonsquamous cell carcinomas (p < 0.001). For squamous cell carcinomas, the immunohistochemical presence of CEA was of marginally negative prognostic value (p = 0.04). DNA ploidy and a high S-phase fraction showed no evidence of prognostic value for stage I tumours, but for stages II and III tumours there was strong evidence of prognostic value (p < 0.001 jointly). The evidence for DNA ploidy was especially strong in stages II and III squamous cell tumours (p = 0.008), and for a high S-phase fraction was strongest in stages II and III nonsquamous cell tumours (p = 0.002).


CONCLUSIONS
AJCC stage remains the most important prognostic indicator from a variety of clinical variables and tumour markers in postoperative patients with resectable NSCLC. For nonsquamous cell lung carcinomas, the presence of peritumoral B lymphocytes was strongly associated with improved survival, suggesting an important role for humoral mediated immunity.
Pelletier
M P
MP
Division of Cardiothoracic Surgery, Royal Victoria Hospital, McGill University Health Centre, Montreal, Que.
Edwardes
M D
MD
Michel
R P
RP
Halwani
F
F
Morin
J E
JE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000401:mortality* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000473:pathology; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011003:Ploidies; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm