CLINICAL RELEVANCE OF TRANSFORMING-GROWTH-FACTOR-ALPHA, EPIDERMAL GROWTH-FACTOR RECEPTOR, P53, AND KI67 IN COLORECTAL LIVER METASTASES AND CORRESPONDING PRIMARY TUMORS

To determine whether the expression of transforming growth factor alph a (TGF-alpha), its receptor (epidermal growth factor receptor [EGFr]), p53 nuclear protein, and proliferation influences prognosis of patien ts with liver metastases, a study was performed in 45 liver metastases and 33 corresponding primary colorectal carcinomas in patients referr ed for liver surgery. The expression of TGF-alpha, EGFr, p53 nuclear p rotein, and proliferation rate was correlated with clinicopathological characteristics and survival after partial liver resection, In liver metastases, TGF-alpha expression was low in 42%, intermediate in 35%, and high in 23%, TGF-alpha expression was higher in liver metastases d erived from lymph node-positive primary carcinomas, in synchronous and in irresectable liver metastases compared with those derived from lym ph node-negative primary carcinomas, metachronous, and resectable live r metastases, Nuclear p53 expression was found in 83% of primary tumor s and 71% of liver metastases. p53 expression did not correlate with t he various clinicopathological characteristics. Ki67 expression was no t associated with clinicopathological characteristics in primary and m etastatic tumors, In the 38 patients in whom a partial liver resection was performed, median survival was 25 months in patients with a highe r TGF-alpha expression in the metastasis than in the primary tumor and 60 months in patients with comparable or lower TGF-alpha expression i n the metastasis than in the primary tumor (P = .036), Median survival after liver resection was 21 months in patients with p53-negative liv er metastases and 58 months in patients with p53-positive metastases ( P = .043). By multivariate analysis, p53 and EGFr expression on liver metastases were the best predictors of disease-free survival after par tial liver resection, with relative risks of 2.38 and 3.33, respective ly. In patients with colorectal liver metastases, referred for liver s urgery, a higher TGF-alpha expression is associated with unfavorable t umor characteristics, whereas p53 and absence of EGFr expression is as sociated with a better survival after partial liver resection.