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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Ishigami
Sumiya
S
First Department of Surgery, Kagoshima University School of Medicine, Kagoshima, Japan. ishiga@med2.kufm.kagoshima-u.ac.jp
Natsugoe
Shoji
S
Tokuda
Koki
K
Nakajo
Akihiro
A
Higashi
Hiroshi
H
Iwashige
Hirohumi
H
Aridome
Kuniaki
K
Hokita
Shuichi
S
Aikou
Takashi
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D017252:CD3 Complex / Q000096:biosynthesis*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018450:Disease Progression; D005260:Female; D005743:Gastrectomy; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain