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Immunochemical Detection of a Small Cell Lung Cancer-associated Ganglioside (FucG_M1) Antigen in Serum¹

Department of Tumor Cell Biology, The Fibiger Institute, Danish Cancer Society [A. J. V., J. Z.], and Department of Oral Diagnosis, The Royal Dental College [H. C.], Copenhagen, Denmark; The Biomembrane Institute, Seattle, Washington 98119 [H. C., T. B. K., T. W., B. S., S. H.]; and Department of Oncology, Bispebjerg Hospital, Copenhagen, Denmark [L. D.]

Recently, the ganglioside FucG_M1 (Fuc1-2Galß1-3GalNAcß1-4[NeuAc2-3]-Galß1-4Glcß1-1Cer) was identified as a small cell lung cancer (SCLC) marker both in chemical and histochemical studies. In order to further determine whether the FucG_M1 ganglioside is shed from the tumor site and consequently is present in the serum of SCLC patients, we produced a series of new monoclonal antibodies raised against FucG_M1 and related glycolipids. Shedding of the FucG_M1 ganglioside was studied both in vitro and in vivo using SCLC cell lines and nude mice xenografts of SCLC cells as model systems, and finally immunochemical analyses were performed on serum samples from patients with SCLC. High-performance thin-layer chromatography immunostaining demonstrated the presence of FucG_M1 in conditioned culture media obtained from FucG_M1-positive SCLC cell lines. Furthermore, tumor extracts of SCLC cell line xenografts in nude mice were positive for the FucG_M1 marker, and more importantly the marker was also present in serum samples from these mice. Twenty serum samples were obtained from patients with histologically verified SCLC. Eight patients had localized disease, and the remaining patients had disseminated cancer involving metastases to other organ sites. Sera from 4 of these patients were clearly positive, and 2 additional cases were found to be weakly positive. The positive patient sera were all from patients with extensive disease. Sera from 12 patients with non-SCLC and 20 healthy individuals were all found to be negative. These results clearly establish the FucG_M1 glycolipid as a potential serum marker of SCLC for which a sensitive immunoassay should be developed and tested using a larger series of serum samples.

¹ This study was supported in part by Project Grants 74-26/89 and 74-26/90 from the Danish Cancer Society and by the National Union against Lung Diseases. Denmark, the Biomembrane Institute, the NIH, the Lundbeck Foundation, Jenny Vissing, and the Danish Medical Research Council.

² To whom requests for reprints should be addressed, at Department of Tumor Cell Biology, The Fibiger Institute, Danish Cancer Society, Ndr. Frihavnsgade 70, DK-2100 Copenhagen, Denmark.

Received 10/ 1/90. Accepted 3/25/91.

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