Oncotarget

Clinical Research Papers:

Investigation of IL-23 (p19, p40) and IL-23R identifies nuclear expression of IL-23 p19 as a favorable prognostic factor in colorectal cancer: a retrospective multicenter study of 675 patients

Melina Helbling, Anne Lukesch, Aladin Haimovici, Eva Karamitopoulou, Martin D. Berger, Marion Hädrich, Makhmud Mallaev, Beat Schnüriger, Viktor H. Koelzer, Heather Dawson, Markus Borner, Rupert Langer, Robert Rosenberg, Ulrich Nitsche, Daniel Inderbitzin, Alessandro Lugli, Mario P. Tschan and Inti Zlobec _

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Oncotarget. 2014; 5:4671-4682. https://doi.org/10.18632/oncotarget.2069

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Abstract

Melina Helbling1, Anne Lukesch2, Aladin Haimovici1, Eva Karamitopoulou1, Martin D. Berger3, Marion Hädrich2, Makhmud Mallaev2, Beat Schnüriger2, Viktor H. Koelzer1, Heather Dawson1, Markus Borner4, Rupert Langer1, Robert Rosenberg5, Ulrich Nitsche6, Daniel Inderbitzin2,7, Alessandro Lugli1, Mario P. Tschan1 and Inti Zlobec1

1 Institute of Pathology, University of Bern, Bern, Switzerland

2 Department of Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland

3 Department of Medical Oncology, Bern University Hospital, Bern, Switzerland

4 Department of Oncology, Hospital Centre Biel, Biel, Switzerland

5 Department of Surgery, Kantonsspital Baden, 5404 Baden, Switzerland

6 Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

7 Department of Surgery, Tiefenau Hospital, Bern, Switzerland

Correspondence:

Inti Zlobec, email:

Keywords: IL-23, colorectal cancer, prognosis, CD8

Received: May 9, 2014 Accepted: June 5, 2014 Published: June 6, 2014

Abstract

IL-23 is a heterodimeric cytokine involved in inflammatory diseases; its role in cancer progression is controversial. Here we analyse the expression of IL-23 subunits (p40 and p19) and IL-23R in colorectal cancer with regard to disease progression, clinical-pathological and molecular aspects. Immunohistochemistry for IL-23p19, IL-23p40, IL-23R and CD8 was performed on a multi-punch tissue microarray of 195 colorectal cancers (cohort 1), matched normal tissue, adenoma and lymph node metastases. Results were compared with clinical-pathological features and CD8+ T-cell counts, then validated on two patient cohorts (cohort 2: n=341, cohort 3: n=139). Cytoplasmic/membranous expression of IL-23 (p19 and p40 subunits) and IL-23R, respectively were over-expressed in carcinomas versus adenomas and normal tissues (p<0.0001) but were reduced in lymph node metastases (p<0.0001). Nuclear IL-23p19 expression was observed in 23.1% and was associated with early TNM stage (p=0.0186), absence of venous (p=0.0124) and lymphatic invasion (p=0.01493), favorable survival (p=0.014) and absence of distant metastasis (p=0.0146; specificity: 100%). This unexpected cellular localization was confirmed by cell fractionation. The beneficial effect of nuclear IL-23p19 was restricted to tumours with CD8+ high counts. Results were validated on Cohorts 2/3. This multicenter study underlines the possible CD8+ dependency and beneficial effect of nuclear IL-23p19 on overall patient survival.


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