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.
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.
Authors: Douglas J Schwartzentruber; David H Lawson; Jon M Richards; Robert M Conry; Donald M Miller; Jonathan Treisman; Fawaz Gailani; Lee Riley; Kevin Conlon; Barbara Pockaj; Kari L Kendra; Richard L White; Rene Gonzalez; Timothy M Kuzel; Brendan Curti; Phillip D Leming; Eric D Whitman; Jai Balkissoon; Douglas S Reintgen; Howard Kaufman; Francesco M Marincola; Maria J Merino; Steven A Rosenberg; Peter Choyke; Don Vena; Patrick Hwu Journal: N Engl J Med Date: 2011-06-02 Impact factor: 91.245
Authors: Kosuke Mima; Reiko Nishihara; Jonathan A Nowak; Sun A Kim; Mingyang Song; Kentaro Inamura; Yasutaka Sukawa; Atsuhiro Masuda; Juhong Yang; Ruoxu Dou; Katsuhiko Nosho; Hideo Baba; Edward L Giovannucci; Michaela Bowden; Massimo Loda; Marios Giannakis; Adam J Bass; Glenn Dranoff; Gordon J Freeman; Andrew T Chan; Charles S Fuchs; Zhi Rong Qian; Shuji Ogino Journal: Cancer Immunol Res Date: 2015-09-29 Impact factor: 11.151
Authors: C Mirjolet; C Charon-Barra; S Ladoire; F Arbez-Gindre; A Bertaut; F Ghiringhelli; A Leroux; D Peiffert; C Borg; J F Bosset; G Créhange Journal: Oncoimmunology Date: 2017-11-27 Impact factor: 8.110