Background and Objectives: The different and unpredictable outcomes in earl
y-stage non-small cell lung cancer patients requires urgent research concer
ning the biological pathway of this neoplasm. Our study investigated the fr
equency of expression and the clinicopathologic and prognostic significance
of a series of biological markers in stage I and II resected non-small cel
l lung cancer.
Methods: A total of 99 cases of pathologic stage I and II were analyzed. Th
e mean follow-up of surviving patients was 41 months. The expressions of th
e following biological markers were tested: bcl-2, p53, Ki-67, angiogenesis
, and tumor vessel invasion. Kaplan-Meier estimates of survival and time to
recurrence were calculated for clinical variables and biological markers u
sing Cox's model for multivariate analysis.
Results: Tumoral vessel invasion was present in 22 (22%) pathologic samples
, the angiogenesis mean value was 37 +/- 13, and median was 35; 13 (13%) pa
tients showed positive immunostaining for bcl-2 oncoprotein. P53 oncoprotei
n expression was present in 48 patients (48.5%). All samples presented Ki-6
7 expression (mean value = 25.3 +/- 19.3, median = 20). The pathologic stag
ing of the tumor was the most important independent prognostic factor for s
urvival (P = 0.037) and for recurrence of disease (P = 0.040). Tumoral vess
el invasion was the only marker with an independent predictive factor for s
urvival and recurrence of disease in the group of patients without lymph no
de involvement (P = 0.02).
Conclusion: Our data do not support a relevant prognostic role for p53, bcl
-2, or Ki-67 immunohistochemical markers in non-small cell cancer. Tumor ve
ssel invasion was an independent predictive factor of poor outcome in the g
roup of patients without lymph node involvement. Pathological stage was con
firmed as the most important independent prognostic factor. (C) 2000 Wiley-
Liss, Inc.