PD-L1 as a Prognostic Factor in Early-Stage Colon Carcinoma within the Immunohistochemical Molecular Subtype Classification

SIMPLE SUMMARY: Colorectal cancer (CRC) is a very heterogeneous disease. Efforts to characterize and search for biomarkers for these patients are currently ongoing in the hope of establishing a more targeted therapeutic approach. The role of PD-1 ligand (PD-L1) expression as a biomarker has not yet been fully elucidated. The Consensus Molecular Subtype classification has been delineated, but although already acknowledged in the most recent international guidelines, it has yet to be implemented in clinical practice. We investigate PD-L1 expression as a biomarker of prognosis in the early-stage setting and integrate it with the Consensus Molecular Subtype (CMS), in an effort to differentiate those patients with a worse prognosis who could potentially benefit from an early, more aggressive treatment. Our results suggest PD-L1 as an independent prognostic factor in early stage setting when assessed by immunohistochemistry. Additionally, PD-L1 expression appears to be a viable biomarker to differentiate patients in the CMS (CMS2/CMS3) who lack a clear prognosis. ABSTRACT: Background. There is a patent need to better characterize early-stage colorectal cancer (CRC) patients. PD-1 ligand (PD-L1) expression has been proposed as a prognostic factor but yields mixed results in different settings. The Consensus Molecular Subtype (CMS) classification has yet to be integrated into clinical practice. We sought to evaluate the prognostic value of PD-L1 expression overall and within CMS in early-stage colon cancer patients, in the hope of assisting treatment choice in this setting. Methods. Tissue-microarrays were constructed from tumor samples of 162 stage II/III CRC patients. They underwent automatic immunohistochemical staining for PD-L1 and the proposed CMS panel. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Results. PD-L1 expression was significantly and independently associated with better prognosis (HR = 0.46 (0.26–0.82), p = 0.009) and was mostly seen in immune cells of the tumor-related stroma. CMS4 five-folds the risk of mortalitycompared with CMS1 (HR = 5.58 (1.36, 22.0), p = 0.034). In the subgroup CMS2/CMS3 analysis, PD-L1 expression significantly differentiated individuals with better OS (p = 0.004) and DFS (p < 0.001). Conclusions. Our study suggests that PD-L1 expression is an independent prognostic factor in patients with stage II/III colon cancer. Additionally, it successfully differentiates patients with better prognosis in the CMS2/CMS3 group and may prove significant for the clinical relevance of the CMS classification.