Is a proliferation index of cancer cells a reliable prognostic factor after hepatectomy in patients with colorectal liver metastases?

BACKGROUND: In spite of many reports focusing on prognostic factors after hepatectomy in patients with colorectal liver metastases, few studies have investigated pathological factors, eg, fibrous pseudocapsulation, growth pattern at the tumor margin, and proliferation activity of cancer cells, other than histological type and surgical margin. The aim of the present study was to investigate whether absence of pseudocapsulation, infiltrative growth pattern of metastases, and higher proliferation of cancer cells shown by Ki-67 immunohistochemical reactivity were associated with poorer survival after hepatectomy among patients with colorectal liver metastases. METHODS: Between 1988 and 1998, 221 patients underwent hepatic resection of colorectal metastases with curative intent in our institution. Pathology analyses were focused on pseudocapsulation of liver metastases, growth pattern at the tumor edge, and Ki-67 labelling index (Ki-67 LI) of cancer cell nuclei. Univariate analyses of survival and of disease-free survival were performed for several clinicopathological factors, and multivariate analyses of survival and disease-free survival were also performed. RESULTS: The univariate survival analyses showed that pseudocapsulation, growth pattern, and Ki-67 LI were significant prognostic factors, besides synchronous versus metachronous occurrence of metastases, carcinoembryonic antigen level before hepatectomy, and number of metastases. A multivariate analysis showed that Ki-67 labeling index was the most reliable prognostic factor of survival. In addition, Ki-67 LI and microscopic growth pattern were multivariately predictive factors of disease-free survival. CONCLUSIONS: This large single-institution study showed that investigation of cancer cell proliferation and pathologic characteristics of the tumor margin are major prognostic factors.