A Tertiary lymphoid structures-based pathological score predicts survival and recurrence in colorectal Cancer patients

Abstract

Background & aim: Colorectal cancer (CRC) is a major global health burden. The immune response within the tumor microenvironment (TME), especially the presence of tertiary lymphoid structures (TLS), plays a critical role in prognosis. However, current prognostic tools often overlook this immune component. This study aimed to characterize TLS in CRC and develop a TLS-score correlating with survival outcomes.

Methods: We conducted a retrospective analysis of 7895 TLS from 806 CRC patients using data from the Finistere Registry of Digestive Tumors. Hematoxylin-eosin-saffron (HES) staining and immunohistochemistry (IHC) were employed for TLS quantification to explore their relationship with survival and recurrence metrics.

Results: Patients with microsatellite instability (MSI) demonstrated higher TLS density and more mature TLS. Both TLS density and maturation showed significant correlations with overall survival (OS) and disease-free survival (DFS). Kaplan-Meier analysis revealed that increased TLS density and GC-like maturation correlated with improved OS and DFS. Our novel pathological TLS score, integrating density and maturation, effectively stratified patients by survival and recurrence risk, distinguishing high-risk individuals (score 0-1-2) with poorer outcomes from low-risk patients (score 3-4) with better prognosis (p < 0.0001), particularly in stage II-III cases.

Conclusion: TLS density and maturation are robust prognostic markers in CRC. The proposed TLS score may aid pathologists in identifying patients at higher recurrence risk and poorer survival, guiding clinical decisions for monitoring and potential adjuvant therapies. Further validation of these findings is essential before clinical implementation.

Keywords: Colorectal cancer; Digital pathology; Prognosis; Tertiary lymphoid structures.