Relationship between early recurrence and micrometastases in the lymph nodes of patients with stage I non-small-cell lung cancer

Objective: This retrospective study was designed to detect occult micrometastases in the lymph nodes with the use of monoclonal anti-cytokeratin reagent, which is specific for epithelial cells but not for lymphocytes or plasmacytes, as well as to assess the relationship between the presence of occult micrometastases in the lymph nodes and an early relapse in patients with stage I non-small-cell lung cancer, Methods: The paraffin-embedded sections of 973 regional lymph nodes from 44 patients with stage I non-small-cell lung cancer were studied. We used CAM-5.2 as the primary monoclonal anti-cytokeratin reagent and an indirect staining technique with the streptavidin-biotin-peroxidase complex method. Results: We identified cytokeratin-positive cells in 31 (70.5%) of 44 patients and in 91 (9.4%) of the 973 lymph nodes. Of these 31 patients with cytokeratin-positive cells, 19 and 12 were restaged as having N1 and N2 disease, respectively, Thirteen patients had recurrent disease at 17 sites during the follow-up. Two of these recurrences were in the mediastinal nodes and the other 15 occurred at distant organs. Twelve of the 13 patients had micrometastatic disease in the regional lymph nodes, Disease-free survival duration was significantly shorter in the patients with micrometastases in the mediastinal lymph nodes than in patients with node-negative disease (p = 0.004), The independence of this prognostic significance was demonstrated by a multivariate analysis. Conclusion: These findings indicate that the detection of occult micrometastases in the mediastinal lymph nodes with monoclonal antibodies to cytokeratin can thus be used to predict an early relapse in patients with stage I non-small-cell lung cancer.