INTRAOPERATIVE DETECTION OF LYMPH NODE MICROMETASTASIS USING A RAPID IMMUNOHISTOCHEMICAL STAINING METHOD IN NON-SMALL CELL LUNG CANCER

Nodal micrometastasis in non-small cell lung cancer (NSCLC) is associated with a poorer survival rate than node-negative disease. Furthermore, lymph node micrometastasis often cannot be detected using conventional hematoxylin and eosin staining of frozen sections ; detection requires additional time-consuming immunohistochemical (IHC) analysis of paraffin-embedded tissue. We previously developed and reported a device that enables us to complete IHC analyses within 11 minutes. In the present study, we used this rapid-IHC protocol with an anti-cytokeratin antibody and analyzed 205 mediastinal lymph nodes dissected during surgery for NSCLC. Although we modified the original rapid-IHC procedure to block endogenous peroxidase activity, which could potentially cause misdiagnosis, the staining was still completed within 19 min. On the basis of conventional histological examination, 7 lymph nodes from 3 patients were deemed positive for micrometastasis. By contrast using hematoxylin and eosin staining, 13 lymph nodes from 7 patients were diagnosed positive on the basis of cytokeratin-detection using routine-IHC, and the same 13 nodes were diagnosed positive on the basis of rapid-IHC. That is, all nodes deemed positive with the routine-IHC procedure were also positive with the rapid-IHC procedure. Assuming the results of the routine-IHC are correct, the sensitivity, specificity and accuracy of rapid-IHC are 100%, 100% and 100%, respectively. These findings demonstrate the utility of our rapid-IHC analysis for intraoperative diagnosis of micrometastasis. However, our findings are limited by the fact that we tested the method using a single antibody at a single institute. Further investigation in multicenter studies will be needed to confirm the utility of this method.