Quantitative analysis of CDX2 protein expression improves its clinical utility as a prognostic biomarker in stage II and III colon cancer.

Autor: den Uil SH; Department of Surgery, Spaarne Gasthuis, Boerhaavelaan 22, 2035 RC, Haarlem, the Netherlands., de Wit M; Department of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands., Slebos RJC; Department of Head & Neck Oncology and Endocrinology, Clinical Science Laboratory, Moffitt Cancer Center, 13131 Magnolia Drive, Tampa, FL, 33612, USA., Delis-van Diemen PM; Department of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands., Sanders J; Department of Pathology, Core Facility Molecular Pathology & Biobanking, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands., Piersma SR; Department of Medical Oncology, OncoProteomics Laboratory, Amsterdam UMC, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands., Pham TV; Department of Medical Oncology, OncoProteomics Laboratory, Amsterdam UMC, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands., Coupé VMH; Department of Epidemiology and Biostatistics, Amsterdam UMC, VU University Medical Center, de Boelelaan 1089a, 1081 HV, Amsterdam, the Netherlands., Bril H; Department of Pathology, Spaarne Gasthuis, Boerhaavelaan 22, 2035 RC, Haarlem, the Netherlands., Stockmann HBAC; Department of Surgery, Spaarne Gasthuis, Boerhaavelaan 22, 2035 RC, Haarlem, the Netherlands., Jimenez CR; Department of Medical Oncology, OncoProteomics Laboratory, Amsterdam UMC, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands., Meijer GA; Department of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands., Fijneman RJA; Department of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands. Electronic address: r.fijneman@nki.nl.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2021 Feb; Vol. 144, pp. 91-100. Date of Electronic Publication: 2020 Dec 17.
DOI: 10.1016/j.ejca.2020.10.029
Abstrakt: 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.
Competing Interests: Conflict of interest statement 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.
(Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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