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Reduced Motility Related Protein-1 (MRP-1/CD9) Gene Expression as a Factor of Poor Prognosis in Non-Small Cell Lung Cancer¹

Department of Surgery, The Center for Adult Diseases of Osaka, Osaka 537 [M. H., K. K., O. D.]; Department of Thoracic Surgery and Department V of Oncology, Kitano Hospital, Tazuke Kofukai Medical Research Institute, 13-3 Kamiyama-cho, Kita-ku, Osaka 530 [T. T., Y. I., M. A., C. H., M. M.]; and Department of Pathology and Tumor Biology, Faculty of Medicine, Kyoto University, Kyoto 606 [T. K.], Japan

Motility related protein-1 (MRP-1) is a transmembrane glycoprotein that is identical to the CD9 antigen. In previous studies, we showed that various types of cultured tumor cells transfected with MRP-1/CD9 cDNA have low motility and diminished metastatic potential to the lung. More recently we used immunohistochemical procedures, immunoblotting, and reverse transcription-PCR to demonstrate that the level of MRP-1/CD9 expression was inversely related to the clinical stage of a given carcinoma of the breast. In addition, we found that the primary tumors of almost 50% of the patients had higher MRP-1/CD9 levels than their respective metastatic lymph nodes. In consideration of these findings, we have now applied reverse transcription-PCR to determine MRP-1/CD9 gene expression in lung cancer. We analyzed tumor tissues of 109 patients: 49 tumors were stage I; 15 were stage II; and 45 were stage III. We found that 67 patients had MRP-1/CD9-positive tumors, and that gene expression was reduced in the tumors of the remaining 42 individuals. The overall rate of survival was strikingly higher among patients with positive tumors than in those whose tumors had reduced gene expression (62.3 versus 34.9%; P < 0.001). This also pertained to patients with adenocarcinomas of the lung (55.4 versus 26.0%; P < 0.001). Multivariate analysis with the Cox regression model indicated that MRP-1/CD9 positivity correlated better with overall survival rate than did other variables, except lymph node status. Our data suggest that low MRP-1/CD9 expression by tumors of the lung may be associated with poor prognosis. It is conceivable that testing for MRP-1/CD9 may identify node-negative lung cancer patients and patients with adenocarcinomas who are at high risk for early disease recurrence.

¹ This work was supported in part by Grants-in-Aid from the Japanese Ministry of Education (to M. M.) and from the Sagawa Foundation for Promotion of Cancer Research (to M. M.).

² To whom requests for reprints should be addressed.

Received 9/26/95. Accepted 11/ 1/95.

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