Immune response to tumor budding ratio: A new potential prognostic score to improve risk stratification for patients with colorectal cancer.

Abstract

e14033 Background: Tumor budding in colorectal cancer is the histologic hallmark of epithelial mesencyhmal transition and is considered an additional prognostic factor by the International Union against Cancer. Abundant tumor budding is associated with lymph node metastasis, vascular invasion and distant metastasis and inversely related to peritumoral lymphocytic inflammation implicating tumor immunity in events occurring at the invasive front. Recently a high CD8+/budding ratio was identified as an independent prognostic factor. The aim of this study was to assess the ratio of various immune cell types to tumor budding ratio in order to define a potential new prognostic score for patients with this disease. Methods: Whole tissue sections from 297 patients with colorectal cancer were cut in series and double immunostaining was performed for CK22 with antibodies directed against CD3, CD8, CD16, CD20, CD21, CD56, CD68, CD138, Foxp3, Granzyme B, and mast cell tryptase. The densest region of tumor budding at the invasive front was identified. Using a 40x objective, the number of tumor buds and positively stained cells for each marker were counted. Results: All protein markers where inversely correlated with the number of tumor buds. After multivariable analysis with pT category, pN category and vascular invasion, a hierarchy of marker/budding ratios identified high Granzyme B+/budding (HR: 0.5 [0.31-0.82; p = 0.006]) as having the strongest positive independent effect on outcome, followed by high CD68+/budding (HR: 0.52 [0.33- 0.84; p = 0.007]), CD8+/budding (HR: 0.54 [0.34-0.84; p = 0.007]), CD16+/budding (HR: 0.56 [0.35-0.9; p = 0.015]), FoxP3+/budding (HR: 0.57 [0.35-0.91; p = 0.019]) and CD3+/budding (HR: 0.58 [0.37-0.9; p = 0.017]). Conclusions: High ratios of CD8+ cytotoxic T- lymphocytes, granzyme B+ or CD68+ cells to tumor budding represent not only a possible mechanism by which budding cells are prevented from disseminating into vessels, but also may lead to an additional prognostic score to improve risk stratification for patients with colorectal cancer. No significant financial relationships to disclose.