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Immunoreactive Gastrin-releasing Peptide as a Specific Tumor Marker in Patients with Small Cell Lung Carcinoma¹

Growth Factor Division [K. M., K. Y., M. S.] and Pathology Division [Y. S.], National Cancer Center Research Institute and Department of Medicine [K. A., N. S.], National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104; the Second Department of Surgery [K. M., Y. M.], Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113; Laboratory of Bioorganic Chemistry [N.Y.], University of Shizuoka School of Pharmaceutical Sciences, Oshika 2-2-1, Shizuoka City, Shizuoka 422, Japan

Gastrin-releasing peptide (GRP) is now known to be a very common product of small cell lung carcinoma (SCLC). With the aim of investigating the possible role of this peptide as a tumor marker of SCLC, we have developed a sensitive radioimmunoassay system for plasma immunoreactive GRP using immune-affinity chromatography for plasma extraction. Plasma immunoreactive GRP levels in control subjects were determined by using 15 ml of plasma as the starting material (minimum concentration detectable, 0.8 pg/ml). The levels in 10 control subjects were (mean ± SD) 1.2 ± 0.27 pg/ml; range, 0.86–1.7 pg/ml. This assay system was applied for the clinical use by using 3 ml of plasma as the starting material (minimum concentration detectable, 4.0 pg/ml). Plasma immunoreactive GRP levels were elevated in SCLC patients at frequencies of 71% in patients with limited disease and 80% in those with extensive disease. Furthermore, a change in the level showed excellent correlation with the therapeutic response. In six patients with complete response who had had elevated levels before treatment, the levels decreased to an undetectable range when the tumor disappeared, and they remained undetectable until 1 month later, when the patients were judged to have achieved complete response. In the partial response group, plasma immunoreactive GRP levels had decreased to an undetectable level in two of three patients, when the patients achieved partial response. In four patients with progressive disease, plasma immunoreactive GRP levels were elevated at the time of the progressive disease judgment, when compared with levels before treatment. The levels in 21 patients with non-SCLC (10 with adenocarcinoma, seven with squamous cell carcinoma and four with large cell carcinoma) were not elevated. These results indicate the plasma immunoreactive GRP level as a useful tumor marker in SCLC patients. It is now believed that GRP can function as an autocrine growth factor for SCLC. The present study suggests that the possible autocrine growth factor could serve as a reliable tumor marker for cancer patients.

¹ This investigation was supported in part by a research grant from the Princess Takamatsu Cancer Research Fund, by a Grant-in-Aid from the Ministry of Health and Welfare for the Comprehensive 10-Year Strategy of Cancer Control, by Grants-in-Aid for Cancer Research (60s, 61-1, 61-8, 62s-1 and 62-26), and by a Research Grant for Intractable Diseases from the Ministry of Health and Welfare.

² To whom requests for reprints should be addressed, at Growth Factor Division, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104, Japan.

Received 6/ 6/88. Revised 10/11/88. Accepted 10/27/88.

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