P-193 - Downregulation of CDX2 is associated with MMR-deficiency but not recurrence in colon cancer

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Colon Cancer
Translational Research
Presenter J. Olsen
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors J. Olsen1, L. Kirkeby2, S. Eiholm2, P. Jess2, I. Gogenur2, J. Troelsen1, M. Espersen1
  • 1Roskilde University, Roskilde/DK
  • 2Roskilde Hospital, Roskilde/DK

Abstract

Introduction

Homeobox genes are often deregulated in cancer. They can have both oncogenic and tumor-suppressing potential. The Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor. It is implicated in differentiation, proliferation, cell-adhesion, and migration. CDX2 has been proposed as a tumor suppressor in colorectal cancer but its role is still controversial. Aim: To investigate CDX2 mRNA and protein expression in relation to clinicopathological characteristics and risk of recurrence in colon cancer.

Methods

Tumor samples were obtained from patients diagnosed with colon cancer, who underwent colon resection at the Department of Surgery, Roskilde University Hospital. Biopsies from both tumor tissue and normal adjacent tissue were fixed in liquid nitrogen for RNA extraction, and formalin for paraffin embedding (FFPE) for immunohistochemical staining. mRNA expression for CDX2 was evaluated with RT-qPCR (n = 97). FFPE sections were stained for MLH1, MSH2, MSH6, PMS2 and CDX2 (n = 191). Patients were followed until recurrence, death of other causes, or for a maximum of five years. Survival analyses were carried out using Cox competing risk regression models.

Results

We found no significant difference in CDX2 mRNA expression between tumor and normal tissue. CDX2 mRNA expression was significantly lower in right-sided tumors (p < 0.05), low differentiated tumors (p < 0.05) and MMR-deficient tumors (p < 0.05), with t-test and ANOVA. Similarly was low/absent CDX2 protein expression associated with right-sided tumors (p < 0.05), low differentiated tumors (p < 0.05) and MMR-deficient tumors (p < 0.01), with Fisher's exact test. Low CDX2 protein or mRNA expression was not associated with risk of recurrence in either unadjusted or adjusted Cox competing risk regression models.

Conclusion

Low CDX2 expression is associated with MMR-deficiency, right-sided tumors and low differentiation at both the mRNA and protein level. This should be kept in mind when using CDX2 as a diagnostic biomarker in identification of tumor cells of unknown/gastrointestinal origin. We found no association between risk of recurrence and CDX2 expression, and conclude that CDX2s potential, as a prognostic biomarker, is probably low.