Mismatch repair phenotype determines the implications of tumor grade and CDX2 expression in stage II–III colon cancer

Hestetun, Kjersti Elvestad; Aasebø, Kristine; Rosenlund, Nina Benedikte; Müller, Yvonne; Dahl, Olav; Myklebust, Mette Pernille

doi:10.1038/s41379-020-0634-9

Cited by 11 publications

(17 citation statements)

References 44 publications

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“…When we noticed the massive enrichment of CDX2 loss within MSI-H tumours, we decided to look into the prognostic relevance of all parameters within microsatellite subgroups of the overall cohort and Stage II/III cancers and observed that CDX2 has a considerable prognostic impact in MSS tumours, but shows no prognostic relevance in MSI-H CRCs, where tumour budding and the different CRC subtypes (but not WHO grade) showed a high prognostic significance. These findings are in line with results from recent studies [ 20 , 25 , 32 , 35 ] and argue that the prognostic relevance of CDX2 expression is tightly connected to the microsatellite status.…”

Section: Discussionsupporting

confidence: 92%

“…UICC Stage II/III) [17]. While the general impact on survival of CDX2 loss has been confirmed by additional studies [18][19][20][21][22][23][24][25][26], it remains to be seen how CDX2 expression is related to the aforementioned HE-based morphologic factors and how the prognostic relevance of CDX2 ranks compared to these central morphologic parameters.…”

Section: Introductionmentioning

confidence: 96%

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Loss of CDX2 in colorectal cancer is associated with histopathologic subtypes and microsatellite instability but is prognostically inferior to hematoxylin–eosin-based morphologic parameters from the WHO classification

et al. 2021

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Background Immunohistochemical loss of CDX2 has been proposed as a biomarker of dismal survival in colorectal carcinoma (CRC), especially in UICC Stage II/III. However, it remains unclear, how CDX2 expression is related to central hematoxylin–eosin (HE)-based morphologic parameters defined by 2019 WHO classification and how its prognostic relevance is compared to these parameters. Methods We evaluated CDX2 expression in 1003 CRCs and explored its prognostic relevance compared to CRC subtypes, tumour budding and WHO grade in the overall cohort and in specific subgroups. Results CDX2-low/absent CRCs were enriched in specific morphologic subtypes, right-sided and microsatellite-instable (MSI-H) CRCs (P < 0.001) and showed worse survival characteristics in the overall cohort/UICC Stage II/III (e.g. DFS: P = 0.005) and in microsatellite stable and left-sided CRCs, but not in MSI-H or right-sided CRCs. Compared with CDX2, all HE-based markers showed a significantly better prognostic discrimination in all scenarios. In multivariate analyses including all morphologic parameters, CDX2 was not an independent prognostic factor. Conclusion CDX2 loss has some prognostic impact in univariate analyses, but its prognostic relevance is considerably lower compared to central HE-based morphologic parameters defined by the WHO classification and vanishes in multivariate analyses incorporating these factors.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 96%

Loss of CDX2 in colorectal cancer is associated with histopathologic subtypes and microsatellite instability but is prognostically inferior to hematoxylin–eosin-based morphologic parameters from the WHO classification

et al. 2021

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“…The study cohorts have been described previously ( 10 ). It includes tissue from the primary tumors of all included patients, 544 in total, with colon cancer stage II and III from two clinical studies.…”

Section: Methodsmentioning

confidence: 99%

“…PD-L1 IHC was performed on a BenchMark Ultra platform with target retrieval using CC1 buffer for 64 min and the Ventana anti-PD-L1 rabbit monoclonal Ab, clone SP 263 (P/N 741-4905, Roche Diagnostics) with 16-min incubation time and Ventana OptiView DAB IHC Detection Kit (P/N 760-700, Roche Diagnostics). MMR and CDX2 IHC has been described previously ( 10 ).…”

Section: Methodsmentioning

confidence: 99%

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Stage-dependent prognostic shift in mismatch repair-deficient tumors: Assessing patient outcomes in stage II and III colon cancer

Hestetun

Rosenlund²,

Stanisavljevic³

et al. 2022

Front. Oncol.

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IntroductionDeficient mismatch repair (dMMR) or high microsatellite instability (MSI-H) is associated with an improved prognosis in colon cancer stage II but poor prognosis in stage IV colon cancer. The clinical significance of dMMR in colon cancer stage III is not established.MethodsTissue microarrays (TMAs) from 544 patients with colon cancer stage II and III with clinicopathological and survival data were stained for mismatch repair (MMR) proteins, CD3, CD8, and programmed death ligand-1 (PD-L1), and programmed death ligand- 1 (PD-L1). Patient outcomes were reviewed.ResultsIn stage III colon cancer, dMMR was a marker of poor disease-free survival (DFS) (Kaplan–Meier, mean survival in months: dMMR: 28.76 (95% CI 18.46–39.05) vs. pMMR 40.91 (37.20–44.63), p=0.014, multivariate Cox regression: hazard ratio (HR) 4.17 (95% CI 2.02–8.61), p<0.001). In stage II colon cancer, there was a tendency toward improved DFS for dMMR patients (dMMR: 57.14 (95% CI 54.66–59.62) vs. pMMR 53.54 (95% CI 51.48–55.60), p=0.015, multivariate Cox regression HR 0.24 (95% CI 0.06-1.04), p=0.057). CD3, CD8, and PD-L1 expression was not associated with prognosis of dMMR patients. Multivariate Cox regression analysis showed a significant interaction between the MMR phenotype and stage (p=0.001).ConclusiondMMR is associated with an improved prognosis in stage II colon cancer but is no longer associated with a favorable prognosis in stage III colon cancer.

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The Prognostic Role of Mismatch Repair Status and CDX-2 Expression with Inflammatory Markers and Pathological Risk Factors in Stage II and III Colon Cancer: Multicenter Real-Life Data

Aydın

Ölmez

Selvi

et al. 2023

J Gastrointest Canc

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Mismatch repair phenotype determines the implications of tumor grade and CDX2 expression in stage II–III colon cancer

Cited by 11 publications

References 44 publications

Loss of CDX2 in colorectal cancer is associated with histopathologic subtypes and microsatellite instability but is prognostically inferior to hematoxylin–eosin-based morphologic parameters from the WHO classification

Loss of CDX2 in colorectal cancer is associated with histopathologic subtypes and microsatellite instability but is prognostically inferior to hematoxylin–eosin-based morphologic parameters from the WHO classification

Stage-dependent prognostic shift in mismatch repair-deficient tumors: Assessing patient outcomes in stage II and III colon cancer

The Prognostic Role of Mismatch Repair Status and CDX-2 Expression with Inflammatory Markers and Pathological Risk Factors in Stage II and III Colon Cancer: Multicenter Real-Life Data

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