Prognostic Significance of Proliferative Activity in pN2 Non–Small-Cell Lung Carcinomas and Their Mediastinal Lymph Node Metastases

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Abstract
To investigate the expression of proliferating cell nuclear antigen (PCNA) in both primary tumor and lymph node metastases of pathologic stage IIIA N2 non–small-cell lung carcinoma (NSCLC) and the relation to prognosis. Although the prognosis of pN2 NSCLC is poor in general, long-term survivors have been reported among patients with completely resected or clinical N0 disease and those with skip metastasis. However, few reports are available on preoperative prognostic predictors. Expression of PCNA is known to be associated with tumor proliferation and is correlated with the prognosis of several carcinomas. Clinicopathologic factors were investigated in relation to prognosis in 76 patients with pathologic stage IIIA pN2 NSCLC from whom resected surgical specimens were available from both the primary tumor and lymph node metastases for evaluation of PCNA expression. A significant correlation was observed between PCNA labeling index in the primary tumor and that in lymph node metastases. The prognosis in patients with PCNA-negative primary tumor (5-year survival rate, 66.0%) was significantly more favorable than that of patients with PCNA-positive primary tumor (5-year survival rate, 21.5%). The prognosis in patients with PCNA-negative metastases was significantly more favorable than that of patients with PCNA-positive metastases. For clinical N2 disease also, the prognosis of patients with PCNA-negative primary tumor was favorable (5-year survival rate, 66.1%). Multivariate analyses showed that PCNA expression and complete resection were significant prognostic factors. Preoperatively diagnosed N2 NSCLC exhibiting negative PCNA expression in primary tumor or lymph node metastases is expected to result in a favorable postoperative prognosis and may be an indication for primary resection.