Immunophenotypic features of metastatic lymph node tumors to predict recurrence in N 2 lung squamous cell carcinoma

Patients with mediastinal lymph node metastasis (N2) in squamous cell carcinoma (Sq CC ) of the lung have poor prognosis after surgical resection of the primary tumor. The aim of this study was to clarify predictive factors of the recurrence of pathological lung Sq CC with N2 focusing on the biological characteristics of both cancer cells and cancer‐associated fibroblasts ( CAF s) in primary and metastatic lymph node tumors. We selected 64 patients with pathological primary lung N2 Sq CC who underwent surgical complete resection and investigated the expressions of four epithelial–mesenchymal transition‐related markers (caveolin, clusterin, E‐cadherin, ZEB 2), three cancer stem cell‐related markers ( ALDH ‐1, CD 44 variant6, podoplanin) of cancer cells, and four markers of CAF s (caveolin, CD 90, clusterin, podoplanin) in both primary and matched metastatic lymph node tumors in the N2 area. In the primary tumors, the expressions of all the examined molecules were not related to recurrence. However, in the metastatic lymph node tumors, high clusterin and ZEB 2 expressions in the cancer cells and high podoplanin expression in the CAF s were significantly correlated with recurrence ( P = 0.03, 0.04, and 0.007, respectively). In a multivariate analysis, only podoplanin expression in the CAF s in metastatic lymph node tumors was identified as a significantly independent predictive factor of recurrence ( P = 0.03). Our study indicated that the immunophenotypes of both cancer cells and CAF s in metastatic lymph node tumors, but not primary tumors, provide useful information for predicting the recurrence of pathological N2 lung Sq CC .