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.
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.
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.
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.