New serum markers for small-cell lung cancer. I. The ganglioside fucosyl-GM1.

The ganglioside fucosyl-GM1 (FucGM1) 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 FucGM1 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 FucGM1 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 FucGM1 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 FucGM1, and 12 of 21 sera from non-SCLC patients were markedly elevated. In SCLC sera, the concentration of FucGM1 in positive sera ranged from 7 to more than 3000 ng/ml FucGM1. None of 20 controls were positive. FucGM1 correlated to organ site involvement of metastases (p = 0.0016). 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.(ABSTRACT TRUNCATED AT 250 WORDS)