Loss of SATB2 Occurs More Frequently Than CDX2 Loss in Colorectal Carcinoma and Identifies Particularly Aggressive Cancers in High-Risk Subgroups

Munich Cancer Registry (MCR), University Hospital of Munich, Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), Ludwig-Maximilian-University (LMU), 81377 Munich, Germany

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Department of Surgery, Klinikum Rechts der Isar, Technical University Munich, 81675 Munich, Germany

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Institute of Pathology, University Hospital Mainz, 55131 Mainz, Germany

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Institute for Translational Cancer Research, German Cancer Consortium (DKTK), Partner Site Munich, 81675 Munich, Germany

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German Cancer Consortium (DKTK), Partner Site Munich, 81675 Munich, Germany

Author to whom correspondence should be addressed.

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These authors contributed equally to this work.

Academic Editors: Marta Baiocchi and Ann Zeuner

Cancers 2021, 13(24), 6177; https://doi.org/10.3390/cancers13246177

Received: 12 November 2021 / Revised: 3 December 2021 / Accepted: 5 December 2021 / Published: 7 December 2021

(This article belongs to the Special Issue In Vitro and In Vivo Models of Colorectal Cancer for Clinical Application)

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The immunohistochemical analysis of Special AT-rich sequence-binding protein 2 (SATB2) is increasingly being used to detect colorectal differentiation. Our study aimed to investigate SATB2 expression levels and the prognostic relevance of SATB2 loss in colorectal carcinoma (CRC), especially in comparison with CDX2, the standard marker of colorectal differentiation. We tested SATB2 expression in 1039 CRCs and identified SATB2 as a strong prognosticator in the overall cohort as well as in specific subcohorts, including high-risk subgroups. Compared to CDX2, SATB2 showed a higher prognostic power but was lost at a much higher frequency, generally rendering SATB2 as the less sensitive marker for colorectal differentiation compared to CDX2.

Abstract

Background: Special AT-rich sequence-binding protein 2 (SATB2) has emerged as an alternative immunohistochemical marker to CDX2 for colorectal differentiation. However, the distribution and prognostic relevance of SATB2 expression in colorectal carcinoma (CRC) have to be further elucidated. Methods: SATB2 expression was analysed in 1039 CRCs and correlated with clinicopathological and morphological factors, CDX2 expression as well as survival parameters within the overall cohort and in clinicopathological subgroups. Results: SATB2 loss was a strong prognosticator in univariate analyses of the overall cohort (p < 0.001 for all survival comparisons) and in numerous subcohorts including high-risk scenarios (UICC stage III/high tumour budding). SATB2 retained its prognostic relevance in multivariate analyses of these high-risk scenarios (e.g., UICC stage III: DSS: p = 0.007, HR: 1.95), but not in the overall cohort (DSS: p = 0.1, HR: 1.25). SATB2 loss was more frequent than CDX2 loss (22.2% vs. 10.2%, p < 0.001) and of higher prognostic relevance with only moderate overlap between SATB2/CDX2 expression groups. Conclusions: SATB2 loss is able to identify especially aggressive CRCs in high-risk subgroups. While SATB2 is the prognostically superior immunohistochemical parameter compared to CDX2 in univariate analyses, it appears to be the less sensitive marker for colorectal differentiation as it is lost more frequently. View Full-Text

Keywords: SATB2; colorectal carcinoma; prognosis; CDX2

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MDPI and ACS Style

Schmitt, M.; Silva, M.; Konukiewitz, B.; Lang, C.; Steiger, K.; Halfter, K.; Engel, J.; Jank, P.; Pfarr, N.; Wilhelm, D.; Foersch, S.; Denkert, C.; Tschurtschenthaler, M.; Weichert, W.; Jesinghaus, M. Loss of SATB2 Occurs More Frequently Than CDX2 Loss in Colorectal Carcinoma and Identifies Particularly Aggressive Cancers in High-Risk Subgroups. Cancers 2021, 13, 6177. https://doi.org/10.3390/cancers13246177

AMA Style

Schmitt M, Silva M, Konukiewitz B, Lang C, Steiger K, Halfter K, Engel J, Jank P, Pfarr N, Wilhelm D, Foersch S, Denkert C, Tschurtschenthaler M, Weichert W, Jesinghaus M. Loss of SATB2 Occurs More Frequently Than CDX2 Loss in Colorectal Carcinoma and Identifies Particularly Aggressive Cancers in High-Risk Subgroups. Cancers. 2021; 13(24):6177. https://doi.org/10.3390/cancers13246177

Chicago/Turabian Style

Schmitt, Maxime, Miguel Silva, Björn Konukiewitz, Corinna Lang, Katja Steiger, Kathrin Halfter, Jutta Engel, Paul Jank, Nicole Pfarr, Dirk Wilhelm, Sebastian Foersch, Carsten Denkert, Markus Tschurtschenthaler, Wilko Weichert, and Moritz Jesinghaus. 2021. "Loss of SATB2 Occurs More Frequently Than CDX2 Loss in Colorectal Carcinoma and Identifies Particularly Aggressive Cancers in High-Risk Subgroups" Cancers 13, no. 24: 6177. https://doi.org/10.3390/cancers13246177

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Loss of SATB2 Occurs More Frequently Than CDX2 Loss in Colorectal Carcinoma and Identifies Particularly Aggressive Cancers in High-Risk Subgroups

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