CD3‐ζchain expression of intratumoral lymphocytes is closely related to survival in gastric carcinoma patients

BACKGROUND Impaired or reduced CD3 zeta chain (CD3‐ζ) expression in T cells has been identified in various cancers and may be associated with an ineffective immune response. The clinical significance of CD3‐ζ chain expression in tumor‐infiltrating lymphocytes (TILs) in gastric carcinoma remains unclear. METHODS The authors immunohistochemically investigated CD3‐ζ expression in TILs in 185 patients who had undergone curative gastrectomy. CD3‐ζ/CD3 epsilon (CD3‐ϵ) ratios were calculated. Patients were divided into two groups: a normal CD3‐ζ group (n = 121) and a reduced CD3‐ζ group (n = 64). Patients with a zeta per epsilon ratio of greater than 66% were placed in the normal CD3‐ζ group. RESULTS Patients in the normal CD3‐ζ group had fewer lymph node metastasis (P < 0.01) and a shallower depth of invasion (P < 0.05) than those in the reduced CD3‐ζ group. The 5‐year survival rate was 72% in the normal CD3‐ζ group, which was significantly better than that in the reduced CD3‐ζ group (55%; P < 0.01). When stratified according to clinical stage, the prognostic value was significantly different only in Stage IV patients. Multivariate analysis showed that CD3‐ζ expression was an independent prognostic factor (P = 0.03) next to depth of invasion and lymph node involvement. CONCLUSIONS Reduced CD3‐ζ expression in TILs was strongly correlated with progressive disease in gastric carcinomas. CD3‐ζ expression in TILs is considered an immunologic, independent prognostic marker in gastric carcinoma patients. CD3‐ζ normalization with cytokine treatment may lead to prolonged survival in advanced gastric carcinoma patients. Cancer 2002;94:1437–42. © 2002 American Cancer Society. DOI 10.1002/cncr.10346 Impaired or reduced CD3 zeta chain (CD3‐ζ) expression in T cells has been identified in various cancers and may be associated with an ineffective immune response. The authors found that reduced CD3‐ζ expression was strongly correlated with progressive disease in gastric carcinomas. CD3‐ζ normalization with cytokine treatment may lead to prolonged survival in advanced gastric carcinoma patients.