PROGNOSTIC-SIGNIFICANCE OF P53 AND RAS P21 EXPRESSION IN NONSMALL CELL LUNG-CANCER

Background. Alterations of the p53 gene are one of the most common gen etic changes in various types of cancer, including lung cancer. Abnorm alities in the ras genes, including point mutations and overexpression , are another common feature in the molecular biology of lung cancer a nd are associated with a poorer prognosis. The authors' purpose was to determine expression of the mutated p53 gene in nonsmall cell lung ca ncer (NSCLC) specimens that were studied for expression of ras p21 and to document whether altered p53 expression was also an important fact or for survival. Methods. Ninety-six patients with NSCLC underwent sur gical resection between 1977 and 1985, 63 of whom received postoperati ve combination chemotherapy. None received radiation therapy. Tumor sp ecimens were analyzed for altered p53 expression by immunohistochemist ry. Univariate and multivariate analyses were performed to assess the association between p53 expression and survival. Results. Fifty-six (5 8%) of 96 tumor specimens showed altered p53 expression, and 91 patien ts were analyzed for survival, Altered p53 expression did not correlat e with clinicopathologic characteristics except for postsurgical patho logic tumor (pT) classification. The patients with altered p53 express ion survived for a significantly shorter period after surgery than tho se without p53 expression, including all patients who underwent resect ion and potentially curative resection (P = 0.02 and P = 0.048, respec tively, generalized Wilcoxon test). Multivariate analysis showed indep endent prognostic significance for altered p53 expression (hazard rati o [HR] = 1.72, P = 0.04) and surgical cure (HR = 4.69, P < 0.001). The combined analysis of mutated p53 and ras p21 expression in the same t umor specimens revealed that patients with p53- and ras p21-negative t umors survived the longest among those with different p53 and ras p21 features (P = 0.005, generalized Wilcoxon test). Conclusion. Altered p 53 expression is a significant and independent negative prognostic fac tor for patients with surgically resected NSCLC. Combined immunohistoc hemical analysis of mutated p53 and ras p21 expression can divide pati ents with NSCLC into more accurate prognostic groups. If the current f indings can be confirmed in larger prospective studies, combined immun ohistochemical analysis of mutated p53 and ras p21 expression can be a useful clinical tool for stratifying patients with NSCLC into accurat e prognostic groups and for identifying the population with a differen t risk of recurrence.