Serum anti-ganglioside IgM antibodies in soft tissue sarcoma: clinical prognostic implications.
OBJECTIVE
Gangliosides are tumor-associated antigens with many biologic functions, including complex interactions with cytokines and other modulators of the immune system. Serum total ganglioside level may be an ideal surrogate marker to predict tumor burden and response to treatment. Antibodies produced against tumor gangliosides may help predict survival. The purpose of this study is to determine whether the serum total ganglioside levels might predict the tumor burden in patients with soft tissue sarcoma, and whether the augmented anti-ganglioside immunoglobulin M (IgM) response might reflect the clinical outcome of these patients.


METHODS
Serum TG levels were measured in the cryopreserved sera by estimating lipid-associated sialic acids from 97 patients before surgical resection of soft tissue sarcoma and from 39 age- and gender-matched healthy volunteers. All sera were analyzed for IgM titers (expressed natural log) by enzyme-linked immunosorbent assay against eight gangliosides (GM1, GM2, GM3, GD3, GD2, GD1a, GD1b, and GT1b). Cox regression was used for univariate and multivariate analyses of the variables affecting progression-free and overall survival.


RESULTS
Serum TG levels were higher in soft tissue sarcoma patients than in healthy individuals (21.8 + 7.7 vs 16.1 + 2.7 mg/dL; P = 0.001). Larger tumors, high histologic grade, and more advanced stage of disease correlated with higher serum total ganglioside levels (P < 0.05). Anti-ganglioside titers to GM3, GD2, and GT1b were significantly higher in patients with soft tissue sarcoma, whereas anti-GD1a and GD1b titers were significantly higher in healthy subjects. The titers of antibodies against GM1, GM2, and GD3 in patients with soft tissue sarcoma were comparable to those of the healthy individuals. When compared with healthy controls, patients with low-grade tumors had higher titers of anti-GT1b, anti-GM3, and anti-GD2 antibodies, and patients with high-grade tumors had higher titers of anti-GT1b and anti-GD2 antibodies. These data suggest that the predominant gangliosides expressed by sarcomas may include GT1b and GD2. In addition, low-grade tumors may express an immunogenic species of GM3. On both univariate and multivariate analyses, augmented anti-GD1a IgM titers, age > 50 years, and retroperitoneal location were predictive of decreased overall survival, whereas augmented anti-GT1b titers were predictive of improved overall survival.


CONCLUSIONS
Serum TG level may be a useful marker of tumor burden and response to treatment for soft tissue sarcoma. Anti-GD1a and anti-GT1b IgM titers predicted survival and may be of therapeutic and prognostic value in the management of soft tissue sarcoma.
Perez
Carlos A
CA
Department of Glycoimmunotherapy, Roy E. Coats Research Laboratories, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, California 90404-2302, USA.
Ravindranath
Mepur H
MH
Soh
Daniel
D
Gonzales
Alexandra
A
Ye
Wei
W
Morton
Donald L
DL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005732:Gangliosides / Q000097:blood* / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D016233:Immunotherapy, Active; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012509:Sarcoma / Q000097:blood* / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis
D000906:Antibodies; D014408:Biomarkers, Tumor; D005732:Gangliosides; D007075:Immunoglobulin M