Colorectal Carcinoma liver Metastases : Immunohistochemical Detection of Hepatic Micrometastases Using Monoclonal Anticytokeratin Antibody

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BACKGROUND : Hepatic metastases from colorectal carcinoma frequently recur after resection and hepatic micrometastases most likely are important in the development of such recurrences. The objectives of the current study were to assess the feasibility of the immunohistochemical detection of hepatic micrometastases from colorectal carcinoma and to determine their clinical significance.METHODS : From January 1981 through December 2003,a total of 129 patients underwent curative hepatic resection for colorectal carcinoma metastases. Multiple tissue sections were cut from the advancing margin of the largest hepatic metastasis in each patient and were stained with an antibody against cytokeratin-20 to detect hepatic micrometastases, which were defined as discrete microscopic cancerous lesions surrounding the dominant metastasis. Proliferation of tumor cells in the hepatic micrometastases was assessed immunohistochemically with Ki-67 staining as an indicator of viability of the tumor cells. T … More he median follow-up period was 127 months.RESULTS : Normal hepatocytes and intrahepatic bile duct epithelia stained negative for cytokeratin-20 in all patients, whereas the largest hepatic tumors stained positive in 114 patients (88%). Among the 114 patients with hepatic tumors that were positive for cytokeratin-20,hepatic micrometastases (a total of 211 lesions) were found immunohistochemically in 77 patients (68%). The presence of hepatic micrometastases was associated with a larger number of macroscopic hepatic metastases (P=0.002) and patients with hepatic micrometastases were found to demonstrate a higher probability of intrahepatic recurrence (P<0.001) compared with those patients without hepatic micrometastases. In addition, patients with hepatic micrometastases demonstrated a worse survival (cumulative 10-year survival rate of 21%) compared with those patients without hepatic micrometastases (cumulative 10-year survival rate of 66%) (P<0.001). Most of the hepatic micrometastases detected (189 of 211 lesions,90%) stained positive for Ki-67.CONCLUSIONS : Immunohistochemical detection of hepatic micrometastases is feasible in patients with colorectal carcinoma liver metastases. Hepatic micrometastasis indicates widespread hepatic involvement and thus predicts an increased risk of intrahepatic recurrence after hepatic resection and a poorer patient prognosis. Most tumor cells in hepatic micrometastases appear to be viable. Less