Immature Stroma and Prognostic Profiling in Colorectal Carcinoma: Development and Validation of Novel Classification Systems

Many pathological characteristics have utility for predicting prognosis in colorectal carcinoma (CRC). Some of the most important include tumor stage (TS), lymph node status (LNS) and tumor budding (TB). Tumor budding is a phenomenon originally described in 1949 as sprouting. TB assessment is not always reliable however, as it is subject to high inter-observer variation. This finding persists despite the current trends for sub-specialty training in surgical pathology. In light of this, new and reproducible histological prognostic markers could change the way we diagnose and manage patients with colorectal carcinoma. Studies have shown that desmoplastic reaction (DR) categorization can actually outperform other conventional prognostic factors, including tumor budding and tumor stage in predicting disease-free survival (DFS). Our study aimed to evaluate and assess the prognostic value of desmoplastic reaction in an American cohort with colorectal cancer using 3 different stromal classification scoring systems. In all three stromal grading systems, immature stroma was the most significant independent prognostic factor in CRC. Currently, none of the reporting protocols for the College of American Pathologists, the Royal College of Pathologists of the United Kingdom, and the Japanese Society for Cancer report on the presence of immature stroma. Importantly, regarding the ability to predict survival outcomes, our novel classification system has the potential to outperform other scoring methodologies.