Useful prognostic panel markers to express the biological tumor status in resected lung adenocarcinomas.

Abstract

Tumor stage and its histological subtype remain the most important predictors of clinical behavior in current pulmonary practice of lung cancer. However, many investigators agree that these parameters are not sufficient to predict which tumor will recur, even after radical curative surgery. Therefore, it is necessary to evaluate the significance of other morphological, biological and molecular parameters beyond TNM classification. Pathological specimens were collected from 45 patients after resection for stage IA (five), stage IB (10), stage IIB (10), stage IIIA (14) and stage IV (six) lung adenocarcinomas. A panel of two morphological (proportion of stroma within the tumor and degree of tumor differentiation), two biological [DNA ploidy and argyrophilic nucleolar organizer region (AgNOR)] and three molecular (immunohistochemical expression of Ki-67, p53 and bcl-2) markers was chosen for analysis of the primary tumor. Life Tables for Survival were used to analyze the individual impact of each variable on survival. Cox proportional hazards model analysis was used to construct an independent tumor status model for cancer recurrence and death. Chi-squared analyses were used to determine the statistically significant relationship among all the variables present in the study. Multivariate analysis demonstrated statistically significant risk for the following markers: AgNOR, p53 and bcl-2, controlled for stages and surgical resection. The immunohistochemical expression of p53 and bcl-2 oncogenes and the expression of AgNOR cell proliferation index are critical values in the progression of lung adenocarcinomas. They can express the biological tumor status and indicate a more accurate prognosis.