CD8/CD45RO T-cell infiltration in endoscopic biopsies of colorectal cancer predicts nodal metastasis and survival

Kölzer, Viktor H.; Lugli, Alessandro; Dawson, Heather; Hädrich, Marion; Berger, Martin D.; Borner, Markus; Mallaev, Makhmudbek; Galván Hernández, José Alberto; Amsler, Jennifer; Schnüriger, Beat; Zlobec, Inti; Inderbitzin, Daniel (2014). CD8/CD45RO T-cell infiltration in endoscopic biopsies of colorectal cancer predicts nodal metastasis and survival. Journal of translational medicine, 12(81), p. 81. BioMed Central 10.1186/1479-5876-12-81

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BACKGROUND AND AIMS: Reliable 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. METHODS: Pre-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. RESULTS: CD8 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 (r[CD45s] = 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. CONCLUSIONS: T-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.

Item Type:

Journal Article (Original Article)

Division/Institute:

?? DCD5A442C3A3E17DE0405C82790C4DE2 ??
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Autopsy
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Kölzer, Viktor; Lugli, Alessandro; Dawson, Heather; Hädrich, Marion; Berger, Martin Dave; Borner, Markus; Galván Hernández, José Alberto; Amsler, Jennifer; Schnüriger, Beat; Zlobec, Inti and Inderbitzin, Daniel

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1479-5876

Publisher:

BioMed Central

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

06 Oct 2014 17:27

Last Modified:

17 Mar 2017 13:56

Publisher DOI:

10.1186/1479-5876-12-81

PubMed ID:

24679169

Uncontrolled Keywords:

Pre-operative biopsies, Colorectal cancer, Pre-operative risk stratification, Immune infiltration, Prognostic factor, Nodal metastasis

BORIS DOI:

10.7892/boris.53079

URI:

https://boris.unibe.ch/id/eprint/53079

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