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Potential predictors for CDX2 expression loss and mismatch repair deficiency in colorectal cancer

CDX2 expression loss is commonly associated with mismatch repair deficiency (dMMR) in colorectal cancer (CRC). However, there are only a few studies that have attempted to correlate CDX2 expression loss with specific MMR genes (MLH1, MSH2, MSH6, PMS2). This is a retrospective study of 327 patients w...

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Autores principales: Vlahović, Ivan, Rajc, Jasmina, Švagelj, Ivan, Šolić, Krešimir, Švagelj, Dražen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266418/
https://www.ncbi.nlm.nih.gov/pubmed/37325467
http://dx.doi.org/10.3389/pore.2023.1610908
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author Vlahović, Ivan
Rajc, Jasmina
Švagelj, Ivan
Šolić, Krešimir
Švagelj, Dražen
author_facet Vlahović, Ivan
Rajc, Jasmina
Švagelj, Ivan
Šolić, Krešimir
Švagelj, Dražen
author_sort Vlahović, Ivan
collection PubMed
description CDX2 expression loss is commonly associated with mismatch repair deficiency (dMMR) in colorectal cancer (CRC). However, there are only a few studies that have attempted to correlate CDX2 expression loss with specific MMR genes (MLH1, MSH2, MSH6, PMS2). This is a retrospective study of 327 patients who underwent surgery due to CRC. Nine patients (2.9%) had two synchronous CRCs, making the total sample 336 CRC. Histopathological data such as tumor type, tumor grade, perineural, lymphatic, and vascular invasion, pT stage, pN stage, peritumoral and intratumoral lymphocytic infiltration were collected and recorded in the database. After immunohistochemical analysis, CDX2 expression, MLH1, MSH2, MSH6, and PMS2 deficiency were also recorded. CDX2 expression loss was detected in 19 out of 336 CRCs (5.9%) and was associated with ascending colon CRC, partially mucinous adenocarcinoma, poorly differentiated carcinoma, and dMMR. Forty-four (13.1%) of CRCs were dMMR. We found a statistically significant association between CDX2 expression loss and MLH1 and PMS2 deficiency. Considering that most expression phenotypes include pairs of MMR genes, we analyzed MLH1/PMS2 and MSH2/MSH6 as heterodimers. Analysis of heterodimers showed a similar result, namely, that MLH1/PMS2 heterodimer deficiency was significantly associated with CDX2 expression loss. We also constructed a regression model for CDX2 expression loss and for dMMR. Poor tumor differentiation and MLH1/PMS2 heterodimer deficiency have been identified as potential predictors for CDX2 expression loss. CRC in the ascending colon and CDX2 expression loss have been identified as positive potential predictors of dMMR with rectal cancer as negative potential predictor of dMMR. Our study showed a significant association between CDX2 expression loss and MLH1 and PMS2 deficiency in CRC. We also managed to produce a regression model for CDX2 expression and showed that poor tumor differentiation and MLH1/PMS2 heterodimer deficiency are independent factors for CDX2 expression loss. We were the first to include CDX2 expression in a regression model for dMMR and showed that CDX2 expression loss can be used as a predictive factor for dMMR, which should be confirmed by further studies.
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spelling pubmed-102664182023-06-15 Potential predictors for CDX2 expression loss and mismatch repair deficiency in colorectal cancer Vlahović, Ivan Rajc, Jasmina Švagelj, Ivan Šolić, Krešimir Švagelj, Dražen Pathol Oncol Res Pathology and Oncology Archive CDX2 expression loss is commonly associated with mismatch repair deficiency (dMMR) in colorectal cancer (CRC). However, there are only a few studies that have attempted to correlate CDX2 expression loss with specific MMR genes (MLH1, MSH2, MSH6, PMS2). This is a retrospective study of 327 patients who underwent surgery due to CRC. Nine patients (2.9%) had two synchronous CRCs, making the total sample 336 CRC. Histopathological data such as tumor type, tumor grade, perineural, lymphatic, and vascular invasion, pT stage, pN stage, peritumoral and intratumoral lymphocytic infiltration were collected and recorded in the database. After immunohistochemical analysis, CDX2 expression, MLH1, MSH2, MSH6, and PMS2 deficiency were also recorded. CDX2 expression loss was detected in 19 out of 336 CRCs (5.9%) and was associated with ascending colon CRC, partially mucinous adenocarcinoma, poorly differentiated carcinoma, and dMMR. Forty-four (13.1%) of CRCs were dMMR. We found a statistically significant association between CDX2 expression loss and MLH1 and PMS2 deficiency. Considering that most expression phenotypes include pairs of MMR genes, we analyzed MLH1/PMS2 and MSH2/MSH6 as heterodimers. Analysis of heterodimers showed a similar result, namely, that MLH1/PMS2 heterodimer deficiency was significantly associated with CDX2 expression loss. We also constructed a regression model for CDX2 expression loss and for dMMR. Poor tumor differentiation and MLH1/PMS2 heterodimer deficiency have been identified as potential predictors for CDX2 expression loss. CRC in the ascending colon and CDX2 expression loss have been identified as positive potential predictors of dMMR with rectal cancer as negative potential predictor of dMMR. Our study showed a significant association between CDX2 expression loss and MLH1 and PMS2 deficiency in CRC. We also managed to produce a regression model for CDX2 expression and showed that poor tumor differentiation and MLH1/PMS2 heterodimer deficiency are independent factors for CDX2 expression loss. We were the first to include CDX2 expression in a regression model for dMMR and showed that CDX2 expression loss can be used as a predictive factor for dMMR, which should be confirmed by further studies. Frontiers Media S.A. 2023-05-31 /pmc/articles/PMC10266418/ /pubmed/37325467 http://dx.doi.org/10.3389/pore.2023.1610908 Text en Copyright © 2023 Vlahović, Rajc, Švagelj, Šolić and Švagelj. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pathology and Oncology Archive
Vlahović, Ivan
Rajc, Jasmina
Švagelj, Ivan
Šolić, Krešimir
Švagelj, Dražen
Potential predictors for CDX2 expression loss and mismatch repair deficiency in colorectal cancer
title Potential predictors for CDX2 expression loss and mismatch repair deficiency in colorectal cancer
title_full Potential predictors for CDX2 expression loss and mismatch repair deficiency in colorectal cancer
title_fullStr Potential predictors for CDX2 expression loss and mismatch repair deficiency in colorectal cancer
title_full_unstemmed Potential predictors for CDX2 expression loss and mismatch repair deficiency in colorectal cancer
title_short Potential predictors for CDX2 expression loss and mismatch repair deficiency in colorectal cancer
title_sort potential predictors for cdx2 expression loss and mismatch repair deficiency in colorectal cancer
topic Pathology and Oncology Archive
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266418/
https://www.ncbi.nlm.nih.gov/pubmed/37325467
http://dx.doi.org/10.3389/pore.2023.1610908
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