Ito Shinya, Miyahara Ryo, Takahashi Rei, Nagai Shinjiro, Takenaka Kazumasa, Wada Hiromi, Tanaka Fumihiro
Department of Thoracic Surgery, Kyoto University, Japan.
Gen Thorac Cardiovasc Surg. 2009 Nov;57(11):591-8. doi: 10.1007/s11748-009-0445-x. Epub 2009 Nov 12.
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.
氨肽酶-N(APN)是一种膜结合蛋白,作为一种锌结合蛋白酶,参与细胞外蛋白水解。APN通过促进侵袭和转移、延长肿瘤细胞存活以及肿瘤血管生成在肿瘤进展中发挥重要作用。
我们通过免疫组织化学评估非小细胞肺癌患者中APN的表达。
在本研究纳入的95例患者中,9例(9.5%)均为腺癌,肿瘤细胞显示APN阳性表达。总共31例(32.6%)和19例(20.0%)患者的肿瘤基质细胞(成纤维细胞)和微血管分别显示APN阳性表达。鳞状细胞癌患者比腺癌患者更频繁地观察到肿瘤基质细胞上的APN表达(P = 0.005)。APN阳性肿瘤基质细胞的平均微血管密度(MVD)为59.9,显著高于APN阴性肿瘤基质细胞(平均MVD 27.4;P = 0.001)。APN阳性和APN阴性肿瘤基质细胞的5年生存率分别为66.0%和69.8%,根据肿瘤基质细胞上的APN状态,患者生存率无差异。
基质细胞上的APN表达主要在鳞状细胞癌中观察到,这可能解释了乌苯美司在鳞状细胞癌术后辅助治疗中的疗效。