To investigate the characteristics of tertiary lymphoid structure (TLS) and their correlation with clinicopathological parameters and prognosis in patients with lymphoepithelioma-like gastric carcinoma (LELGC).

A total of 114 patients with LELGC were selected from Changzhou First People's Hospital from February 2009 to December 2020. Histopathological review and TLS maturity and density analysis were performed on 114 surgical specimens. Then, the expression of CD3, CD4, CD8, CD20, CD21, and PD-L1 in lymphocytes in tumor tissues was detected by immunohistochemical staining. Finally, Kaplan-Meirer survival analysis and COX regression analysis were used to examine the impact of TLS on patient prognosis.

TLS was mainly distributed in the tumor stroma and concentrated in the invasive edge area of the tumor. T lymphocyte distribution was dominant in tumor tissues with mature TLS (mTLS), and B lymphocyte distribution was dominant in tumor tissues with non-mTLS. The average tumor diameter (t=2.727, P=0.007), positive rate of vascular and nerve invasion (χ²=4.672, P=0.031), lymph node metastasis rate (χ²=8.920, P=0.003), and incidence of clinical stage Ⅲ/Ⅳ (χ²=15.360, P<0.001) in the mTLS group were significantly lower than those of the non-mTLS group. The incidence of pathological T3/T4 stage (depth of invasion) in the TLS high-density group was 80.0% (44/55), which was significantly higher than that of the TLS low-density group (53.3%, 35/59) (χ²=5.721, P=0.017). Univariate COX regression analysis showed that tumor diameter (hazard ratio [HR]=1.177, P=0.011), lymph node metastasis (HR=11.873, P=0.016), vascular nerve invasion (HR=4.430, P=0.007), pathological T-stage (depth of invasion, HR=13.706, P=0.011), clinical stage (HR=6.387, P<0.001), and TLS maturity (HR=0.225, P=0.001) were significantly correlated with the prognosis of patients. Multivariate COX regression analysis showed that T stage (depth of invasion, HR=9.765, P=0.028), clinical stage (HR=3.523, P=0.014), and TLS maturity (HR=0.228, P=0.001) were significantly correlated with the prognosis of patients. Kaplan-Meirer survival analysis showed that the average survival time of patients in the mTLS group was (72.0±4.7) months, which was significantly longer than that of the non-mTLS group (33.7±5.5 months) (χ²=14.063, P<0.001). The average survival time of patients in the TLS high-density group was (65.4±5.0) months, which was significantly longer than that of the non-mTLS group (51.8±6.5 months) (χ²=5.482, P=0.019). mTLS and high density TLS had a positive effect on overall survival.

TLS in LELGC is mainly distributed in the invasive edge region of tumors. Tumor tissues with mTLS are dominated by T lymphocyte distribution, whereas tumor tissues with non-mTLs are dominated by B lymphocyte distribution. High-density and mature TLS in LELGC may have a positive impact on the prognosis of patients, providing new predictors and targets for the prognosis and treatment of patients.