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Effects of CDX2 on prognosis and chemotherapy responsiveness in mismatch repair‐deficient colorectal cancer

BACKGROUND: Caudal‐related homeobox transcription factor 2 (CDX2) is an intestine‐specific transcription factor implicated in tumour differentiation, proliferation, cell adhesion and migration. Negative CDX2 status (CDX2−) is associated with worse prognosis in colorectal cancer and may identify high...

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Autores principales: Ryan, É. J., Creavin, B., Khaw, Y. L., Kelly, M. E., Mohan, H. M., Geraghty, R., Ryan, E. J., Kennelly, R., Hanly, A., Martin, S. T., Fennelly, D., McDermott, R., Gibbons, D., O'Connell, P. R, Sheahan, K., Winter, D. C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6253792/
https://www.ncbi.nlm.nih.gov/pubmed/30511046
http://dx.doi.org/10.1002/bjs5.91
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author Ryan, É. J.
Creavin, B.
Khaw, Y. L.
Kelly, M. E.
Mohan, H. M.
Geraghty, R.
Ryan, E. J.
Kennelly, R.
Hanly, A.
Martin, S. T.
Fennelly, D.
McDermott, R.
Gibbons, D.
O'Connell, P. R
Sheahan, K.
Winter, D. C.
author_facet Ryan, É. J.
Creavin, B.
Khaw, Y. L.
Kelly, M. E.
Mohan, H. M.
Geraghty, R.
Ryan, E. J.
Kennelly, R.
Hanly, A.
Martin, S. T.
Fennelly, D.
McDermott, R.
Gibbons, D.
O'Connell, P. R
Sheahan, K.
Winter, D. C.
author_sort Ryan, É. J.
collection PubMed
description BACKGROUND: Caudal‐related homeobox transcription factor 2 (CDX2) is an intestine‐specific transcription factor implicated in tumour differentiation, proliferation, cell adhesion and migration. Negative CDX2 status (CDX2−) is associated with worse prognosis in colorectal cancer and may identify high‐risk stage II disease that benefits from adjuvant chemotherapy. This observational study investigated whether CDX2− is associated with prognosis or response to chemotherapy in the mismatch repair‐deficient (dMMR) phenotype of colorectal cancer. METHODS: Patients with resectable dMMR colorectal cancer were eligible for inclusion. The prognostic and predictive value of CDX2 expression on the presence of lymph node metastasis (LNM) and survival was investigated. CDX2 status was determined via immunohistochemistry using the Leica Bond™ CDX2 (clone EP25) ready‐to‐use primary antibody. RESULTS: Some 235 of 238 consecutive dMMR tumours were assessed for CDX2 status. CDX2− was observed in 15·7 per cent of colorectal cancer. Interobserver agreement was excellent (κ = 0·863; P < 0·001). CDX2− was significantly associated with female sex, increased size, advanced stage, worse conventional and poorly differentiated cluster (PDC) grade, mucinous morphology, perineural and lymphovascular invasion, and pN status (all P ≤ 0·038). CDX2− was not associated with LNM or survival in multivariable analysis. Independent predictors of LNM were PDC grade (odds ratio (OR) 4·12, 95 per cent c.i. 1·76 to 9·63; P = 0·001) and extramural venous invasion (OR 3·79, 1·62 to 8·85; P = 0·002). Budding (hazard ratio (HR) 2·79, 95 per cent c.i. 1·60 to 4·87; P < 0·001), pT status (HR 3·59, 1·29 to 10·01; P = 0·015) and adjuvant chemotherapy (HR 2·07, 1·15 to 3·74; P = 0·016) were independently associated with worse disease‐free survival. CONCLUSION: CDX2− does not confer a worse prognosis in the dMMR phenotype of colorectal cancer. The MMR status of patients with colorectal cancer should be determined before assessing CDX2 status.
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spelling pubmed-62537922018-12-03 Effects of CDX2 on prognosis and chemotherapy responsiveness in mismatch repair‐deficient colorectal cancer Ryan, É. J. Creavin, B. Khaw, Y. L. Kelly, M. E. Mohan, H. M. Geraghty, R. Ryan, E. J. Kennelly, R. Hanly, A. Martin, S. T. Fennelly, D. McDermott, R. Gibbons, D. O'Connell, P. R Sheahan, K. Winter, D. C. BJS Open Original Articles BACKGROUND: Caudal‐related homeobox transcription factor 2 (CDX2) is an intestine‐specific transcription factor implicated in tumour differentiation, proliferation, cell adhesion and migration. Negative CDX2 status (CDX2−) is associated with worse prognosis in colorectal cancer and may identify high‐risk stage II disease that benefits from adjuvant chemotherapy. This observational study investigated whether CDX2− is associated with prognosis or response to chemotherapy in the mismatch repair‐deficient (dMMR) phenotype of colorectal cancer. METHODS: Patients with resectable dMMR colorectal cancer were eligible for inclusion. The prognostic and predictive value of CDX2 expression on the presence of lymph node metastasis (LNM) and survival was investigated. CDX2 status was determined via immunohistochemistry using the Leica Bond™ CDX2 (clone EP25) ready‐to‐use primary antibody. RESULTS: Some 235 of 238 consecutive dMMR tumours were assessed for CDX2 status. CDX2− was observed in 15·7 per cent of colorectal cancer. Interobserver agreement was excellent (κ = 0·863; P < 0·001). CDX2− was significantly associated with female sex, increased size, advanced stage, worse conventional and poorly differentiated cluster (PDC) grade, mucinous morphology, perineural and lymphovascular invasion, and pN status (all P ≤ 0·038). CDX2− was not associated with LNM or survival in multivariable analysis. Independent predictors of LNM were PDC grade (odds ratio (OR) 4·12, 95 per cent c.i. 1·76 to 9·63; P = 0·001) and extramural venous invasion (OR 3·79, 1·62 to 8·85; P = 0·002). Budding (hazard ratio (HR) 2·79, 95 per cent c.i. 1·60 to 4·87; P < 0·001), pT status (HR 3·59, 1·29 to 10·01; P = 0·015) and adjuvant chemotherapy (HR 2·07, 1·15 to 3·74; P = 0·016) were independently associated with worse disease‐free survival. CONCLUSION: CDX2− does not confer a worse prognosis in the dMMR phenotype of colorectal cancer. The MMR status of patients with colorectal cancer should be determined before assessing CDX2 status. John Wiley & Sons, Ltd 2018-07-24 /pmc/articles/PMC6253792/ /pubmed/30511046 http://dx.doi.org/10.1002/bjs5.91 Text en © 2018 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of BJS Society Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Ryan, É. J.
Creavin, B.
Khaw, Y. L.
Kelly, M. E.
Mohan, H. M.
Geraghty, R.
Ryan, E. J.
Kennelly, R.
Hanly, A.
Martin, S. T.
Fennelly, D.
McDermott, R.
Gibbons, D.
O'Connell, P. R
Sheahan, K.
Winter, D. C.
Effects of CDX2 on prognosis and chemotherapy responsiveness in mismatch repair‐deficient colorectal cancer
title Effects of CDX2 on prognosis and chemotherapy responsiveness in mismatch repair‐deficient colorectal cancer
title_full Effects of CDX2 on prognosis and chemotherapy responsiveness in mismatch repair‐deficient colorectal cancer
title_fullStr Effects of CDX2 on prognosis and chemotherapy responsiveness in mismatch repair‐deficient colorectal cancer
title_full_unstemmed Effects of CDX2 on prognosis and chemotherapy responsiveness in mismatch repair‐deficient colorectal cancer
title_short Effects of CDX2 on prognosis and chemotherapy responsiveness in mismatch repair‐deficient colorectal cancer
title_sort effects of cdx2 on prognosis and chemotherapy responsiveness in mismatch repair‐deficient colorectal cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6253792/
https://www.ncbi.nlm.nih.gov/pubmed/30511046
http://dx.doi.org/10.1002/bjs5.91
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