Clinical Significance of Occult Micrometastases in Colorectal Cancer

Lee, Suk Hwan; Kim, Tae Young; Kim, Yoon Wha; Koh, Suck Hwan; Yoon, Choong; Oh, Soo Myung; Lee, Kee Hyung

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.