Stromal aminopeptidase N expression: correlation with angiogenesis in non-small-cell lung cancer

Abstract

Aminopeptidase-N (APN) is a membranebound protein that acts as a zinc-binding protease and participates in extracellular proteolysis. APN plays important roles in tumor progression through promoting invasion and metastasis, prolonging survival of tumor cells, and tumor angiogenesis. We evaluated APN expression in non-small-cell lung cancer patients by immunohistochemistry. Of the 95 patients reviewed in the present study, 9 (9.5%), all with adenocarcinoma (Ad), showed positive APN expression on the tumors' cells. In all, 31 (32.6%) and 19 (20.0%) patients showed positive APN expression on the tumors' stromal cells (fibroblasts) and microvessels, respectively. APN expression on the tumors' stromal cells was more frequently observed in squamous cell carcinoma patients than in adenocarcinoma patients (P = 0.005). The mean microvessel density (MVD) for APNpositive tumor stromal cells was 59.9, which was significantly higher than that for APN-negative tumor stromal cells (mean MVD 27.4; P = 0.001). The 5-year survival rates for APN-positive and APN-negative tumor stromal cells were 66.0% and 69.8%, respectively, showing no difference in patient survival according to APN status on the tumors' stromal cells. That APN expression on stromal cells was observed predominantly in squamous cell carcinoma may account for the efficacy of ubenimex in the postoperative adjuvant setting for squamous cell carcinoma.