Clinical significance of aminopeptidase N in non-small cell lung cancer.
OBJECTIVE
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.


METHODS
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).


CONCLUSIONS
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.
Tokuhara
Takahiro
T
Department of Thoracic Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan.
Hattori
Noboru
N
Ishida
Hisao
H
Hirai
Tatsuya
T
Higashiyama
Masahiko
M
Kodama
Ken
K
Miyake
Masayuki
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018826:CD13 Antigens / Q000032:analysis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000201:enzymology* / Q000601:surgery; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000201:enzymology; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015996:Survival Rate
D018826:CD13 Antigens