Identification of occult micrometastases in pericolic lymph nodes of Duke's B colorectal cancer patients using monoclonal antibodies against cytokeratin and CC49. Correlation with long-term survival

Abstract

Background: Patients with transmurally invasive, lymph node negative colorectal carcinoma (Dukes' B) have a 5-year survival rate ranging from 53.9% to 84.9%. The authors postulate that patients with Dukes' B colon cancer who die of their disease have occult micrometastases in their pericolic lymph nodes at the time of original diagnosis. In an attempt to identify these occult micrometastases, pericolic lymph nodes from Dukes' B colon cancer resections were stained retrospectively with antibodies against cytokeratin (anti-keratin AE1/AE3, Boehringer Mannheim, Indianapolis, IN) and CC49 (a second-generation monoclonal antibody directed against TAG-72.

Methods: The authors reviewed all Dukes' B (transmurally invasive, lymph node negative) primary colorectal carcinoma resection specimens from the surgical pathology files of the Ohio State University Hospitals between 1984 and 1987. Survival data were obtained from the Tumor Registry of the Arthur G. James Cancer Hospital and Research Institute, Columbus, Ohio. The results were analyzed by univariate and multivariate analysis.

Results: Fifty cases with 568 lymph nodes (11.3 per case) were examined with each antibody using standard immunoperoxidase techniques. Positive staining for cytokeratin was seen in 14 patients (33 lymph nodes), 6 of whom died of colon cancer within 66 months (43%). Only 1 of the 36 patients with cytokeratin-negative lymph nodes died of colon cancer over the same time period (3%, P = 0.0009 univariate, P = 0.0013 multivariate). There was no significant difference in survival between the CC49-positive and CC49-negative groups.

Conclusion: Immunoperoxidase techniques are capable of identifying micrometastatic disease in lymph nodes missed by routine hematoxylin and eosin staining. Further, the presence of cytokeratin-positive cells within lymph nodes correlated with a significantly poorer prognosis. Therefore, cytokeratin staining of pericolic lymph nodes in patients with Dukes' B colorectal cancer is recommended. Larger multicenter studies are needed, however, to confirm these results and to evaluate the appropriateness of adjuvant chemotherapy in patients whose disease is upstaged by immunohistochemical staining.