Clinical relevance of transforming growth factor α, epidermal growth factor receptor, p53, and Ki67 in colorectal liver metastases and corresponding primary tumors

Abstract

To determine whether the expression of transforming growth factor ␣ (TGF-␣), its receptor (epidermal growth factor receptor [EGFr]), p53 nuclear protein, and proliferation influences prognosis of patients with liver metastases, a study was performed in 45 liver metastases and 33 corresponding primary colorectal carcinomas in patients referred for liver surgery. The expression of TGF-␣, EGFr, p53 nuclear protein, and proliferation rate was correlated with clinicopathological characteristics and survival after partial liver resection. In liver metastases, TGF-␣ expression was low in 42%, intermediate in 35%, and high in 23%. TGF-␣ expression was higher in liver metastases derived from lymph node-positive primary carcinomas, in synchronous and in irresectable liver metastases compared with those derived from lymph node-negative primary carcinomas, metachronous, and resectable liver metastases. Nuclear p53 expression was found in 83% of primary tumors and 71% of liver metastases. p53 expression did not correlate with the various clinicopathological characteristics. Ki67 expression was not associated with clinicopathological characteristics in primary and metastatic tumors. In the 38 patients in whom a partial liver resection was performed, median survival was 25 months in patients with a higher TGF-␣ expression in the metastasis than in the primary tumor and 60 months in patients with comparable or lower TGF-␣ expression in the metastasis than in the primary tumor (P ‫؍‬ .036). Median survival after liver resection was 21 months in patients with p53-negative liver 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 diseasefree survival after partial liver resection, with relative risks of 2.38 and 3.33, respectively. In patients with colorectal liver metastases, referred for liver surgery, a higher TGF-␣ expression is associated with unfavorable tumor characteristics, whereas p53 and absence of EGFr expression is associated with a better survival after partial liver resection. (HEPATOLOGY 1998;28:971-979.)Colorectal carcinoma is the second-leading cause of cancer deaths in the Western community. Of all colorectal cancer patients, about 50% will die within 5 years after diagnosis. 1 At the time of initial diagnosis, 15% to 25% of patients present with synchronous liver metastases. 1 It is estimated that overall, only 5% of patients who develop liver metastases of colorectal carcinomas are amenable to partial liver resection. 2 Despite intentionally curative liver resections, only 20% to 30% of these patients have a disease-free 5-year survival. [3][4][5] Furthermore, in patients with recurrences after liver resection, these recurrences often appear early after liver surgery, with the liver being a frequent site of initial failure. 5,6 In the animal model, tumor growth can be influenced by growth factors produced by the tumor cells and by growth factors generated by the organ that harbors the m...

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