The intratumoral distribution influences the prognostic impact of CD68- and CD204-positive macrophages in non-small cell lung cancer

Abstract Objective Tumor-associated macrophages(TAMs) are believed to influence tumor progression and the prognosis of patients. The purpose of this study was to clarify the correlation between the TAM density or location and the clinicopathological features of non-small-cell lung cancer (NSCLC) as well as to explore the prognostic impact of TAMs in NSCLC. Materials and methods CD68- and CD204-positive macrophages were detected in tumor islets, tumor stromaand alveolar space in 297 patients with NSCLC using immunochemistry. The clinicopathological and genetic factors surveyed were the disease-free survival, age, gender, smoking status, histological type, disease stage, histological grade, pleural invasion, lymph node metastasis, EGFR gene mutations and ALK rearrangements. Results There were significantly more CD68-positive macrophages than CD204-positive macrophages in each location of the tumor islets, tumor stromaand alveolar spaces, and they were strongly correlated ( P EGFR gene status were significantly correlated with a higher density of CD68- and CD204-positive TAMs in tumor stroma( P P  > 0.05 each). Furthermore, survival analysis revealed that a high number of CD68- and CD204-positive TAMs in tumor stroma, but not in tumor islets or alveolar space, was a significant prognostic factor for the disease-free survival time of NSCLC ( P Conclusion The tumor stromais the most suitable intratumoral area for the evaluation of TAMs in the setting of the prognostic prediction of NSCLC patients. CD204-positive TAMs are the preferable marker for prognostic prediction in NSCLC, especially in lung adenocarcinoma.