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Clinical Significance of Aminopeptidase N in Non–Small Cell Lung Cancer

Authors' Affiliations: ¹ Department of Thoracic Surgery and Department V of Oncology, Kitano Hospital, Tazuke Kofukai Medical Research Institute; ² Department of Thoracic Surgery, Osaka Medical College; and ³ Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

Requests for reprints: Masayuki Miyake, Department of Thoracic Surgery and Department V of Oncology, Kitano Hospital, Tazuke Kofukai Medical Research Institute, 2-4-20, Ohgimachi, Kita-ku, Osaka 530-8480, Japan. Phone: 81-6-6312-8816; Fax: 81-6-6312-8816; E-mail: miyakem{at}kitano-hp.or.jp.

Purpose: The aim of our study is to investigate the mechanism of metastasis, to detect novel metastasis-associated molecules, and to evaluate the molecules from the point of view of clinical application. A monoclonal antibody MH8-11, which we established, recognizes a glycoprotein that is identical to aminopeptidase N (APN/CD13). APN/CD13 degrades the extracellular matrix, while it is also involved in cell motility and improves angiogenesis.

Experimental Design: We investigated the expression of APN/CD13 in 194 cases of non–small cell lung cancer (NSCLC) by immunohistochemical analyses and reverse transcription-PCR assay to determine the significance of this prognostic factor; 95 tumors were stage I, 36 were stage II, 39 were stage IIIA, and 24 were stage IIIB. Moreover, we investigated that the relationship between the expression of APN/CD13 and angiogenesis and prognosis for patients with NSCLC.

Results: We found a correlation between the expression of APN/CD13 and angiogenesis (r = 0.659; P < 0.0001). In the 194 patients with NSCLC, we found 68 patients to be APN/CD13⁺ and 126 patients to be APN/CD13^–. The 5-year survival rate in patients with APN/CD13⁺ tumors was significantly lower than in those whose tumors had negative APN/CD13 (48.3% versus 67.1%; P = 0.0001).

Conclusion: Our data suggest the expression of APN/CD13 for patients with NSCLC to be associated with a poor prognosis and angiogenesis. This is the first study to show the relationship between the expression of APN/CD13 and the prognosis of patients with NSCLC. The inhibition of APN/CD13 may be an effective new molecular target therapy for patients with NSCLC.