TY - JOUR
T1 - Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer
AU - Salama, P.
AU - Phillips, Michael
AU - Grieu, F.
AU - Morris, Melinda
AU - Zeps, Nikolajs
AU - Joseph, David
AU - Platell, Cameron
AU - Iacopetta, Barry
PY - 2009
Y1 - 2009
N2 - Purpose To determine the prognostic significance of FOXP3+ lymphocyte (Treg) density in colorectal cancer compared with conventional histopathologic features and with CD8+ and CD45RO+ lymphocyte densities. Patients and Methods Tissue microarrays and immunohistochemistry were used to assess the densities of CD8+, CD45RO+, and FOXP3+ lymphocytes in tumor tissue and normal colonic mucosa from 967 stage II and stage III colorectal cancers. These were evaluated for associations with histopathologic features and patient survival. Results FOXP3+ Treg density was higher in tumor tissue compared with normal colonic mucosa, whereas CD8+ and CD45RO+ cell densities were lower. FOXP3+ Tregs were not associated with any histopathologic features, with the exception of tumor stage. Multivariate analysis showed that stage, vascular invasion, and FOXP3+ Treg density in normal and tumor tissue were independent prognostic indicators, but not CD8+ and CD45RO+. High FOXP3+ Treg density in normal mucosa was associated with worse prognosis (hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.13; P = .019). In contrast, a high density of FOXP3+ Tregs in tumor tissue was associated with improved survival (HR = 0.54; 95% CI, 0.38 to 0.77; P = .001). Conclusion FOXP3+ Treg density in normal and tumor tissue had stronger prognostic significance in colorectal cancer compared with CD8+ and CD45RO+ lymphocytes. The finding of improved survival associated with a high density of tumor-infiltrating FOXP3+ Tregs in colorectal cancer contrasts with several other solid cancer types. The inclusion of FOXP3+ Treg density may help to improve the prognostication of early-stage colorectal cancer.
AB - Purpose To determine the prognostic significance of FOXP3+ lymphocyte (Treg) density in colorectal cancer compared with conventional histopathologic features and with CD8+ and CD45RO+ lymphocyte densities. Patients and Methods Tissue microarrays and immunohistochemistry were used to assess the densities of CD8+, CD45RO+, and FOXP3+ lymphocytes in tumor tissue and normal colonic mucosa from 967 stage II and stage III colorectal cancers. These were evaluated for associations with histopathologic features and patient survival. Results FOXP3+ Treg density was higher in tumor tissue compared with normal colonic mucosa, whereas CD8+ and CD45RO+ cell densities were lower. FOXP3+ Tregs were not associated with any histopathologic features, with the exception of tumor stage. Multivariate analysis showed that stage, vascular invasion, and FOXP3+ Treg density in normal and tumor tissue were independent prognostic indicators, but not CD8+ and CD45RO+. High FOXP3+ Treg density in normal mucosa was associated with worse prognosis (hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.13; P = .019). In contrast, a high density of FOXP3+ Tregs in tumor tissue was associated with improved survival (HR = 0.54; 95% CI, 0.38 to 0.77; P = .001). Conclusion FOXP3+ Treg density in normal and tumor tissue had stronger prognostic significance in colorectal cancer compared with CD8+ and CD45RO+ lymphocytes. The finding of improved survival associated with a high density of tumor-infiltrating FOXP3+ Tregs in colorectal cancer contrasts with several other solid cancer types. The inclusion of FOXP3+ Treg density may help to improve the prognostication of early-stage colorectal cancer.
U2 - 10.1200/JCO.2008.18.7229
DO - 10.1200/JCO.2008.18.7229
M3 - Article
C2 - 19064967
VL - 27
SP - 186
EP - 192
JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
SN - 0732-183X
IS - 2
ER -