@article{55b8fb09d9d14f3c893a3ca300557e7a,
title = "Quantitative analysis of CDX2 protein expression improves its clinical utility as a prognostic biomarker in stage II and III colon cancer",
abstract = "Aim: Better stratification of patients with stage II and stage III colon cancer for risk of recurrence is urgently needed. The present study aimed to validate the prognostic value of CDX2 protein expression in colon cancer tissue by routine immunohistochemistry and to evaluate its performance in a head-to-head comparison with tandem mass spectrometry–based proteomics. Patient and methods: CDX2 protein expression was evaluated in 386 stage II and III primary colon cancers by immunohistochemical staining of tissue microarrays and by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis using formalin-fixed paraffin-embedded tissue sections of a matched subset of 23 recurrent and 23 non-recurrent colon cancers. Association between CDX2 expression and disease-specific survival (DSS) was investigated. Results: Low levels of CDX2 protein expression in stage II and III colon cancer as determined by immunohistochemistry was associated with poor DSS (hazard ratio [HR] = 1.97 (95% confidence interval [CI]: 1.26–3.06); p = 0.002). Based on analysis of a selected sample subset, CDX2 prognostic value was more pronounced when detected by LC-MS/MS (HR = 7.56 (95% CI: 2.49–22.95); p < 0.001) compared to detection by immunohistochemistry (HR = 1.60 (95% CI: 0.61–4.22); p = 0.34). Conclusion: This study validated CDX2 protein expression as a prognostic biomarker in stage II and III colon cancer, conform previous publications. CDX2 prognostic value appeared to be underestimated when detected by routine immunohistochemistry, probably due to the semiquantitative and subjective nature of this methodology. Quantitative analysis of CDX2 substantially improved its clinical utility as a prognostic biomarker. Therefore, development of routinely applicable quantitative assays for CDX2 expression is needed to facilitate its clinical implementation.",
keywords = "Biomarkers, CDX2, Colon cancer, Immunohistochemistry, Prognosis, Proteomics",
author = "{den Uil}, {Sjoerd H.} and {de Wit}, Meike and Slebos, {Robbert J.C.} and {Delis-van Diemen}, {Pien M.} and Joyce Sanders and Piersma, {Sander R.} and Pham, {Thang V.} and Coup{\'e}, {Veerle M.H.} and Herman Bril and Stockmann, {Hein B.A.C.} and Jimenez, {Connie R.} and Meijer, {Gerrit A.} and Fijneman, {Remond J.A.}",
note = "Funding Information: G.A.M. reports receiving non-financial support from Exact Sciences, Sysmex, Sentinel CH. SpA, Personal Genome Diagnostics (PGDX), grants from CZ (OWM Centrale Zorgverzekeraars groep Zorgverzekeraar u. a), other support from Hartwig Medical Foundation, Royal Philips, GlaxoSmithKline, Keosys SARL, Open Clinica LLC, Roche Diagnostics Nederland BV, The Hyve BV, Open Text, SURFSara BV, Vancis BV and CSC Computer Sciences BV, outside the submitted work; In addition, G.A.M. has several patents pending. R.J.A.F. reports receiving grants and non-financial support from Personal Genome Diagnostics, grants from MERCK BV, non-financial support from Pacific Biosciences and Cergentis BV, outside the submitted work; In addition, R.J.A.F. has several patents pending. Funding Information: S.H.d.U. was financially supported by ?Stichting Chirurg en Onderzoek Kennemerland? (The Netherlands), VUmc Cancer Center Amsterdam, The Netherlands (project grant CCA 2011-5-06). This work was performed within the framework of the Center for Translational Molecular Medicine, DeCoDe project (030?101) and TraIT (05T-401). Funding Information: S.H.d.U. was financially supported by “ Stichting Chirurg en Onderzoek Kennemerland” (The Netherlands), VUmc Cancer Center Amsterdam, The Netherlands (project grant CCA 2011-5-06 ). This work was performed within the framework of the Center for Translational Molecular Medicine, DeCoDe project (030–101) and TraIT (05T-401). Publisher Copyright: {\textcopyright} 2020 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = feb,
doi = "https://doi.org/10.1016/j.ejca.2020.10.029",
language = "English",
volume = "144",
pages = "91--100",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
}