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Cancer. 2002 Mar 1;94(5):1437-42.

CD3-zetachain expression of intratumoral lymphocytes is closely related to survival in gastric carcinoma patients.

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  • 1First Department of Surgery, Kagoshima University School of Medicine, Kagoshima, Japan.



Impaired or reduced CD3 zeta chain (CD3-zeta) expression in T cells has been identified in various cancers and may be associated with an ineffective immune response. The clinical significance of CD3-zeta chain expression in tumor-infiltrating lymphocytes (TILs) in gastric carcinoma remains unclear.


The authors immunohistochemically investigated CD3-zeta expression in TILs in 185 patients who had undergone curative gastrectomy. CD3-zeta/CD3 epsilon (CD3-epsilon) ratios were calculated. Patients were divided into two groups: a normal CD3-zeta group (n = 121) and a reduced CD3-zeta group (n = 64). Patients with a zeta per epsilon ratio of greater than 66% were placed in the normal CD3-zeta group.


Patients in the normal CD3-zeta group had fewer lymph node metastasis (P < 0.01) and a shallower depth of invasion (P < 0.05) than those in the reduced CD3-zeta group. The 5-year survival rate was 72% in the normal CD3-zeta group, which was significantly better than that in the reduced CD3-zeta 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-zeta expression was an independent prognostic factor (P = 0.03) next to depth of invasion and lymph node involvement.


Reduced CD3-zeta expression in TILs was strongly correlated with progressive disease in gastric carcinomas. CD3-zeta expression in TILs is considered an immunologic, independent prognostic marker in gastric carcinoma patients. CD3-zeta normalization with cytokine treatment may lead to prolonged survival in advanced gastric carcinoma patients.

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