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

Background: Tumor stage and its histological subtype remain the most import ant predictors of clinical behavior in current pulmonary practice of lung c ancer. However, many investigators agree that these parameters are not suff icient to predict which tumor will recur, even after radical curative surge ry. Therefore, it is necessary to evaluate the significance of other morpho logical, biological and molecular parameters beyond TNM classification. Methods: Pathological specimens were collected from 45 patients after resec tion for stage IA (five), stage IB (10), stage IIB (10), stage IIIA (14) an d stage IV (six) lung adenocarcinomas. A panel of two morphological (propor tion of stroma within the tumor and degree of tumor differentiation), two b iological [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 Sur vival were used to analyze the individual impact of each variable on surviv al. Cox proportional hazards model analysis was used to construct an indepe ndent tumor status model for cancer recurrence and death. Chl-squared analy ses were used to determine the statistically significant relationship among all the variables present in the study. Results: Multivariate analysis demonstrated statistically significant risk for the following markers: AgNOR, p53 and bcl-2, controlled for stages and surgical resection. Conclusions: 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 t umor status and indicate a more accurate prognosis.