CD8-CD45RO T-cell infiltration in endoscopic biopsies of colorectal cancer predicts nodal metastasis and survivalReport as inadecuate

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Journal of Translational Medicine

, 12:81

Cancer microenvironment


Background and aimsReliable prognostic markers based on biopsy specimens of colorectal cancer CRC are currently missing. We hypothesize that assessment of T-cell infiltration in biopsies of CRC may predict patient survival and TNM-stage before surgery.

MethodsPre-operative biopsies and matched resection specimens from 130 CRC patients treated from 2002-2011 were included in this study. Whole tissue sections of biopsy material and primary tumors were immunostained for pancytokeratin and CD8 or CD45RO. Stromal s and intraepithelial i T-cell infiltrates were analyzed for prediction of patient survival as well as clinical and pathological TNM-stage of the primary tumor.

ResultsCD8 T-cell infiltration in the preoperative biopsy was significantly associated with favorable overall survival CD8i p = 0.0026; CD8s p = 0.0053 in patients with primary CRC independently of TNM-stage and postoperative therapy HR CD8i = 0.55 95% CI: 0.36-0.82, p = 0.0038; HR CD8s = 0.72 95% CI: 0.57-0.9, p = 0.0049. High numbers of CD8i in the biopsy predicted earlier pT-stage p < 0.0001 as well as absence of nodal metastasis p = 0.0015, tumor deposits p = 0.0117, lymphatic p = 0.008 and venous invasion p = 0.0433 in the primary tumor. Infiltration by CD45ROs cells was independently associated with longer survival HR = 0.76 95% CI: 0.61-0.96, p = 0.0231 and predicted absence of venous invasion p = 0.0025. CD8 counts were positively correlated between biopsies and the primary tumor r = 0.42; p < 0.0001 and were reproducible between observers ICC CD8i = 0.95, ICC CD8s = 0.75. For CD45RO, reproducibility was poor to moderate ICC CD45i = 0.16, ICC CD45s = 0.49 and correlation with immune infiltration in the primary tumor was fair and non-significant rCD45s = 0.16; p = 0.2864. For both markers, no significant relationship was observed with radiographic T-stage, N-stage or M-stage, indicating that assessment of T-cells in biopsy material can add additional information to clinical staging in the pre-operative setting.

ConclusionsT-cell infiltration in pre-operative biopsy specimens of CRC is an independent favorable prognostic factor and strongly correlates with absence of nodal metastasis in the resection specimen. Quantification of CD8i is highly reproducible and allows superior prediction of clinicopathological features as compared to CD45RO. The assessment of CD8i infiltration in biopsies is recommended for prospective investigation.

KeywordsPre-operative biopsies Colorectal cancer Pre-operative risk stratification Immune infiltration Prognostic factor Nodal metastasis AbbreviationsCEACarcinoembryoenic antigen

CRCColorectal cancer

EMTEpithelial-mesenchymal transition

HPFHigh-power fields

HRHazard ratio

ICCIntra-class correlation coefficient

ITBIntra-tumoral budding

REMARKREporting recommendations for tumor MARKer prognostic studies

SITCSociety for Immunotherapy of Cancer

TNM-stageTumor Node Metastasis stage.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-12-81 contains supplementary material, which is available to authorized users.

Viktor H Koelzer, Alessandro Lugli contributed equally to this work.

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Author: Viktor H Koelzer - Alessandro Lugli - Heather Dawson - Marion Hädrich - Martin D Berger - Markus Borner - Makhmudbek Mal


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