Published in Cancer Detection and Prevention 1994; 18(3):221-230.

New Serum Markers for Small-Cell Lung Cancer I. The Ganglioside Fucosyl-GM(1)

Annette Vangsted, MDa, Lars Drivsholm, MDb, Elo Andersen, MDa, Tina Pallesen, MScc, Jesper Zeuthen, DSca, Hakan Wallin, PhDa

aDanish Cancer Society Dept of Tumor Cell Biology and Environmental Carcinogenesis, bState Univ Hospital Dept of Oncology, and cUniv of Copenhagen School of Dentistry, Copenhagen, Denmark

Address all correspondence and reprint requests to: Annette Vangsted, MD, The Wallenberg Laboratory, Univ of Lund, Box 7031, S-220 07 Lund, Sweden Part II of this article, The Neural Cell Adhesion Molecule, NCAM, will appear in the next issue of this journal

ABSTRACT: The ganglioside fucosyl-GM, (FucGM(1)) has been suggested as a marker for small-cell lung cancer (SCLC). Immunohistochemical analyses have shown the expression of the ganglioside in tumors in 75 to 90% of patients with SCLC. We have demonstrated that the ganglioside is shedded from SCLC cells both in vitro and in vivo, and that the antigen can be detected in sera from SCLC patients by an immunochemical analysis. The FucGM, antigen has recently been shown to act as a target for antibody- dependent cellular cytotoxicity. This may provide a rationale for developing immunotherapy against SCLC. We used an immunoassay based on the scintillation proximity assay to analyze the concentrations of FucGM, in sera from 112 SCLC patients, 21 patients with non-SCLC, 4 patients with other cancer forms, and 20 healthy controls. Sera were collected at the time of diagnosis before initiation of chemotherapy. The expression of FucGM, was related to age, sex, blood group of the patient, and to the stage of disease and organ site involvement of metastases. The sera of 50% of the patients with SCLC were positive for FucGM(1), and 12 of 21 sera from non-SCLC patients were markedly elevated. In SCLC sera, the concentration of FucGM, in positive sera ranged from 7 to more than 3000 ng/ml FucGM(1). None of 20 controls were positive. FucGM, correlated to organ site involvement of metastases (p = 0.00 1 6). The ganglioside was detected both at significantly higher concentrations (p = 0.0005) and in significantly more patients (p = 0.0026) with metastases to both the liver and bone marrow, compared to patients with metastases to the liver only. A strong trend (p = 0.055) was found toward a better survival of patients negative for FucGM(1). Elevated levels of the ganglioside FucGM(1) were detected in the serum of half of the patients with SCLC and non-SCLC. In some patients, the concentration was 1000-fold higher than that of healthy controls. In sera from SCLC patients, the expression of the ganglioside correlated with organ site involvement of metastases, and a strong trend was found toward a poorer survival of patients expressing this ganglioside marker. It is therefore possible that serum FucGM, may be used in evaluating adjuvant treatment approaches of SCLC, and may have importance as a prognostic marker for SCLC.

KEY WORDS: fucosyl-GM(1), ganglioside, lung cancer, serum, .