The interactive effect of Ras, HER2, P53 and Bcl-2 expression in predicting the survival of non-small cell lung cancer patients

In patients with non-small cell lung cancer (NSCLC), tumor expression of P2 1-Ras, HER2, P53, and Bcl-2 has been reported as independent predictors of prognosis. However, the prognostic information carried by these proteins ha s usually been determined separately, and their potential interaction has n ot been taken into account. We conducted immunostaining for P21-Ras, HER2, P53 and Bcl-2 on 238 cases of NSCLC in a Korean population with 203 squamou s cell carcinomas, and 35 adenocarcinomas. P21-Ras, HER2, P53 or Bcl-2 was expressed at high levels in 54.6, 42.0, 18.1 and 71.8% of the NSCLC studied , respectively. A total of 59 tumors (24.8%) expressed only one protein, wh ile 70 (29.4%) expressed two, 59 (24.8%) expressed three, and 17 tumors (7. 1%) expressed all four proteins. Univariate analysis testing the associatio n of marker expression with survival found Bcl-2 expression to be significa ntly associated with a poor prognosis, as well as the co-expression of Bcl- 2 + HER2, Bcl-2 + HER2 + P53, and Bcl-2 + HER2 + P53 + P21-ras with an incr easing hazard ratio. By multivariate analysis controlling for age, tumor st age and tumor type, only the combination of Bcl-2 + HER2 expression was an independent marker of poor prognosis (hazard ratio = 1.91, P = 0.003). Thus , a prospective analysis of the co-expression of Bcl-2 + HER2 in NSCLC pati ents may identify patients with a poor prognosis who may benefit from more aggressive therapy. (C) 1998 Elsevier Science Ireland Ltd. All rights reser ved.