NEW SERUM MARKERS FOR SMALL-CELL LUNG-CANCER .1. THE GANGLIOSIDE FUCOSYL-GM(1)

The ganglioside fucosyl-GM, (FucGM1) has been suggested as a marker fo r small-cell lung cancer (SCLC). Immunohistochemical analyses have sho wn the expression of the ganglioside in tumors in 75 to 90% of patient s 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 det ected in sera from SCLC patients by an immunochemical analysis. The Fu cGM1 antigen has recently been shown to act as a target for antibody-d ependent cellular cytotoxicity. This may provide a rationale for devel oping 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 expres sion of FucGM1 was related to age, sex, blood group of the patient, an d to the stage of disease and organ site involvement of metastases. Th e 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 s era, the concentration of FucGM1 in positive sera ranged from 7 to mor e than 3000 ng/ml FucGM1. None of 20 controls were positive. FucGM1 co rrelated to organ site involvement of metastases (p = 0.001 6). The ga nglioside was detected both at significantly higher concentrations (p = 0.0005) and in significantly more patients (p = 0.0026) with metasta ses to both the liver and bone marrow, compared to patients with metas tases to the liver only. A strong trend (p = 0.055) was found toward a better survival of patients negative for FucGM1. Elevated levels of t he ganglioside FucGM1 were detected in the serum of half of the patien ts with SCLC and non-SCLC. In some patients, the concentration was 100 0-fold higher than that of healthy controls. In sera from SCLC patient s, the expression of the ganglioside correlated with organ site involv ement of metastases, and a strong trend was found toward a poorer surv ival of patients expressing this ganglioside marker. It is therefore p ossible that serum FucGM1 may be used in evaluating adjuvant treatment approaches of SCLC, and may have importance as a prognostic marker fo r SCLC.