Abstract
Background: A tertiary lymphoid structure (TLS) is a crucial component of the tumor microenvironment, which reflects the anti-tumor immune response in the host. The aim of the present study was to carry out a histopathological evaluation for TLS and assess its prognostic value in gastric cancer (GC).Methods: A total of 1,033 cases that have received a gastrectomy were reviewed, including 914 in the primary cohort and 119 in the validation cohort. TLS was assessed by optical microscopy and verified by immunohistochemistry. A total of five histopathological evaluation methods were compared in the primary cohort and validated in the validation cohort. In addition, MECA-79 and CD21 were used to verify the accuracy of the histopathological scoring system for TLS. The association among TLS, clinicopathological parameters, and patient prognosis was analyzed.Results: TLS as assessed by morphology and immunohistochemistry were significantly correlated and consistent. The morphological evaluation of TLS was accurate. Typically, the high level of TLS was significantly correlated with tumor size (P = 0.047), histological grade (P = 0.039), pTN stage (P = 0.044), and WHO subtype (P < 0.001). In addition, TLShi was a positive indicator of overall survival, as determined by Kaplan–Meier survival (P = 0.038) and multivariate Cox regression analyses (hazard ratio = 0.794, 95% CI: 0.668–0.942, P = 0.008). According to the results, TLShi had a positive effect on the primary cohort patients with pTN stages II and III (P = 0.027, P = 0.042).Conclusions: The histopathological evaluation of TLS was accurate. Diagnosis based solely on hematoxylin and eosin staining of the sections did not easily distinguish tumor-associated TLS. The density of TLS in the center of the tumor was found to be more indicative of patient prognosis than TLS in the invasive margin, with the levels of total TLS shown to best correlate with overall survival in patients with advanced-stage GC.
Highlights
The tumor microenvironment (TME) is the internal environment where a tumor develops and where a functional complex of interactions among tumor cells, stromal cells, and tumor-infiltrating lymphocytes (TIL) takes place
The patient inclusion criteria were as follows: (i) patients pathologically diagnosed with primary gastric adenocarcinoma, (ii) patients who were naïve to preoperative chemotherapy or radiotherapy, (iii) patients with adequate formalin-fixed and paraffinembedded (FFPE) tissue blocks, (iv) patients with at least one slide containing the tumor invasive margin (IM), and (v) patients with complete medical records and follow-up information
The analysis was conducted based on data from the primary cohort
Summary
The tumor microenvironment (TME) is the internal environment where a tumor develops and where a functional complex of interactions among tumor cells, stromal cells, and tumor-infiltrating lymphocytes (TIL) takes place. The TME status reflects the interaction between the host immune response and tumor progression. TIL is a key component in TME that reflects the anti-tumor immune response in the host. It is crucial for suppressing cancer progression and has implications for the success of the host anti-tumor immune response against certain solid tumors [1,2,3]. The mechanisms that promote an anti-tumor immune response, as well as the association between TLS and patient prognosis, in gastric cancer (GC) remain unclear [13]. A tertiary lymphoid structure (TLS) is a crucial component of the tumor microenvironment, which reflects the anti-tumor immune response in the host. The aim of the present study was to carry out a histopathological evaluation for TLS and assess its prognostic value in gastric cancer (GC)
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