Tumor-Infiltrating Lymphocytes and Tumor-Stroma Ratio on Early-Stage Cervix Carcinoma: Prognostic Value of Two Distinct Morphological Patterns of Microenvironment.

Background Tumor progression is influenced by the complex network of different cellular elements that make up its microenvironment. Tumor-infiltrating lymphocytes (TILs) and stroma characteristics reflect two faces of the intricate mechanisms involved in the tumor-host interaction and can be easily evaluated by routine histological examination. Their prognostic value could be demonstrated in different tumor tumor types, but they are poorly explored in cervical cancer. Methodology In this retrospective study, we analyzed the association of TILs, tumor-stroma ratio (TSR), and pattern of stromal fibroblasts with prognosis and classical clinicopathological variables. We studied 61 patients with early-stage cervical cancer. We reviewed histological type, tumor grade, Silva pattern of invasion for adenocarcinomas, tumor thickness, depth of stromal invasion, lymph vascular space invasion, and lymph node status. The median follow-up was 37.77 months (range 4.77 to 112.37 months). Results The TSR did not correlate with any clinicopathological features or disease-free and overall survival. On the other hand, the reactive pattern of stroma composed of larger fibroblasts and less collagenization was associated with the FIGO IB2 stage (p=0.04), larger tumor (p=0.03), and deeper infiltration (p=0.005). There were more recurrences in the group of reactive stroma (33.13% vs. 11.5%), although the difference did not reach statistical significance. Reactive stroma was associated with lower survival free of recurrence (p=0.05) and overall survival (p=0.009). High TILs were associated with squamous cell type (p=0.003), higher tumor grade (p=0.02), and more LVSI (p=0.02). Tumors with higher TILs presented higher free recurrence interval (p=0.06) and overall survival (p=0.03). No association was observed between stroma characteristics and TILs. Conclusions Our study suggested that although immune activation and stromal changes are important features of microenvironment remodeling during tumoral progression, they are independent, following distinct carcinogenetic pathways. Pathological assessment of stroma characteristics and TILs adds significant prognostic information and demonstrates how a simple routine laboratory assessment can generate a better understanding of biological phenomena.