Clinical Significance of Occult Micrometastases in Colorectal Cancer

ABSTRACT

BACKGROUND: One of the most important prognostic factors in colorectal cancer is lymph node metastasis, which predicts a reduced survival time. Although lymph node metastases were not detected by a conventional hematoxylin-eosin stain technique, 20 to 30 percent of patients fail long-term survival on account of a local or systemic recurrence. Recurrent disease in these patients is believed to develop from occult tumor in lymph nodes. PURPOSE: The authors have conducted an immunohistochemical study with two different antibodies against cytokeratin to identify occult micrometastases in lymph nodes which were diagnosed as tumor negative by conventional histopathology. METHODS: Paraffin blocks of sixty-five patients with colorectal cancer (T2/3, N0, M0) after a curative resection between January 1991 and December 1993 at Kyung-Hee University Hospital were stained with avidin-biotin-peroxidase complex technique using two monoclonal antibodies (anti-cytokeratin AE1/AE3 and anti-cytokeratin No. 20, DAKO, Hamburg, Germany). To assess the clinical correlation between micrometastasis in lymph node and patients survial, 5-year disease-free survival rates were calculated by Kaplan-Meier method and the significance of the differences was estimated by the log-rank test. P values <0.05 were taken to be significant. RESULTS: Of the sixty-five patients with 1133 lymph nodes, tumor cells detected by anti-cytokeratin AE1/AE3 and anti-cytokeratin No. 20, were 2.4 percent (27/1133) and 3.4 percent (38/1133), respectively. Micrometastases were detected in twenty-six patients (40.0 percent). The histologic stage of four cytokeratin positive cases was upstaged from T2, N0, M0 to T2, N1/2, M0, and twenty-two of T3, N0, M0 to T3, N1/2, M0. Cytokeratin-positive cases showed statistically significant recurrence rate (42.3 percent) compared to that of cytokeratin -negative cases (17.9 percent)(x2 test, p=0.032). With the median follow-up of 62 months, 5-year disease-free survival rates of the micrometastses negative and positive cases were 81.7 percent and 61.3 percent, respectively (p=0.0438). CONCLUSIONS: In conclusion, immunohistochemical technique to identify the occult micrometastases in lymph nodes overlooked in conventional histopathology is a useful staging method to anticipate a recurrence and a prognosis more precisely.