Tumor-Infiltrating CD45RO+-Cell Density, but Not CD3+, CD8+, or FOXP3+-Cell Density, Has a Prognostic Role in Colorectal Cancer, Independent of Molecular Features.
Katsuhiko Nosho, Glenn Dranoff, Charles Fuchs, Shuji Ogino. Dana-Farber Cancer Institute, Boston, MA; Brigham and Women's Hospital, Boston, MA
Background: The abundance of tumor-infiltrating T-cells is associated with microsatellite instability (MSI) and good prognosis in colorectal cancer. Because molecular features including MSI, the CpG island methylator phenotype (CIMP), and BRAF mutation have been associated with prognosis, potential confounding by these molecular features needs to be controlled when assessing the prognostic significance of T-cells.
Design: We utilized a database of 768 colorectal cancers with clinical and molecular annotations. Using tissue microarray and automated Ariol image analysis system, we quantified densities of CD3+, CD8+, CD45RO+ and FOXP3+-cells within neoplastic epithelial areas and within stromal areas.
We used Cox proportional hazard models to compute mortality hazard ratio (HR), adjusting for clinical and molecular features including KRAS, BRAF, and PIK3CA mutations, MSI, CIMP and LINE-1 hypomethylation.
Results: The densities of CD45RO+ and FOXP3+-cells in epithelial areas (and stromal areas) were significantly associated with patient survival in Kaplan-Meier analyses (log-rank p<0.0004) (Q1-Q4 indicating the lowest to highest quartiles in Fig. 2) and univariate regression analyses (Ptrend<0.0001).
In multivariate analyses, tumor-infiltrating CD45RO+-cell density, but not CD3+, CD8+ or FOXP3+-cell density, was associated with survival (multivariate HR=0.51; 95% CI, 0.32-0.80; p=0.0032). In multivariate linear regression, MSI-high (p<0.0001) and tumor LINE-1 hypermethylation (p=0.0013) were independently associated with CD45RO+-cell density. Nonetheless, the survival benefit associated with CD45RO+-cells was independent of MSI and LINE-1 status.
Conclusions: Tumor-infiltrating CD45RO+-cell density is a prognostic factor, associated with longer survival of colorectal cancer patients independent of tumor molecular features.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 50, Wednesday Morning