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An Insight into Deficient Mismatch Repair Colorectal Cancer Screening in a Romanian Population—A Bi-Institutional Pilot Study

Background and Objectives: Colorectal cancer (CRC) can be classified as mismatch-repair-deficient (dMMR) with high levels of microsatellite instability (MSI-H), or mismatch-repair-proficient (pMMR) and microsatellite stable (MSS). Approximately 15% of patients have microsatellite instability (MSI)....

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Autores principales: Lungulescu, Cristina, Croitoru, Vlad Mihai, Volovat, Simona Ruxandra, Cazacu, Irina Mihaela, Turcu-Stiolica, Adina, Gheonea, Dan Ionut, Sur, Daniel, Lungulescu, Cristian Virgil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401048/
https://www.ncbi.nlm.nih.gov/pubmed/34441055
http://dx.doi.org/10.3390/medicina57080847
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author Lungulescu, Cristina
Croitoru, Vlad Mihai
Volovat, Simona Ruxandra
Cazacu, Irina Mihaela
Turcu-Stiolica, Adina
Gheonea, Dan Ionut
Sur, Daniel
Lungulescu, Cristian Virgil
author_facet Lungulescu, Cristina
Croitoru, Vlad Mihai
Volovat, Simona Ruxandra
Cazacu, Irina Mihaela
Turcu-Stiolica, Adina
Gheonea, Dan Ionut
Sur, Daniel
Lungulescu, Cristian Virgil
author_sort Lungulescu, Cristina
collection PubMed
description Background and Objectives: Colorectal cancer (CRC) can be classified as mismatch-repair-deficient (dMMR) with high levels of microsatellite instability (MSI-H), or mismatch-repair-proficient (pMMR) and microsatellite stable (MSS). Approximately 15% of patients have microsatellite instability (MSI). MSI-H tumors are associated with a high mutation burden. Monoclonal antibodies that block immune checkpoints can induce long-term durable responses in some patients. Pembrolizumab is the first checkpoint inhibitor approved in the EU to treat dMMR–MSI-H metastatic CRC. Materials and Methods: Our study assesses the regional variability of MSI-H colorectal cancer tumors in Romania. Formalin-fixed, paraffin-embedded (FFPE) tissue blocks containing tumor samples from 90 patients diagnosed with colorectal cancer were collected from two tertiary referral Oncology Centers from Romania. Tissues were examined for the expression loss of MMR proteins (MLH1, PMS2, MSH2, MSH6) using immunohistochemistry or MSI status using polymerase chain reaction (PCR), respectively. Results: MSI-H was detected in 19 (21.1%) patients. MSI-H was located more in ascending colon (36.8% vs. 9.9%, p-value = 0.0039) and less in sigmoid (5.3% vs. 33.8%, p-value = 0.0136) than MSS patients. Most patients were stage II for MSI-H (42.1%) as well as for MSS (56.3%), with significant more G1 (40.9% vs. 15.8%, p-value = 0.0427) for MSS patients. Gender, N stage, and M stage were identified as significant prognostic factors in multivariate analysis. MSI status was not a statistically significant predictor neither in univariate analysis nor multivariate analysis. Conclusion: Considering the efficacy of PD-1 inhibitor in metastatic CRC with MSI-H or dMMR, and its recent approval in EU, it is increasingly important to understand the prevalence across tumor stage, histology, and demographics, since our study displayed higher regional MSI-H prevalence (21%) compared to the literature.
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spelling pubmed-84010482021-08-29 An Insight into Deficient Mismatch Repair Colorectal Cancer Screening in a Romanian Population—A Bi-Institutional Pilot Study Lungulescu, Cristina Croitoru, Vlad Mihai Volovat, Simona Ruxandra Cazacu, Irina Mihaela Turcu-Stiolica, Adina Gheonea, Dan Ionut Sur, Daniel Lungulescu, Cristian Virgil Medicina (Kaunas) Article Background and Objectives: Colorectal cancer (CRC) can be classified as mismatch-repair-deficient (dMMR) with high levels of microsatellite instability (MSI-H), or mismatch-repair-proficient (pMMR) and microsatellite stable (MSS). Approximately 15% of patients have microsatellite instability (MSI). MSI-H tumors are associated with a high mutation burden. Monoclonal antibodies that block immune checkpoints can induce long-term durable responses in some patients. Pembrolizumab is the first checkpoint inhibitor approved in the EU to treat dMMR–MSI-H metastatic CRC. Materials and Methods: Our study assesses the regional variability of MSI-H colorectal cancer tumors in Romania. Formalin-fixed, paraffin-embedded (FFPE) tissue blocks containing tumor samples from 90 patients diagnosed with colorectal cancer were collected from two tertiary referral Oncology Centers from Romania. Tissues were examined for the expression loss of MMR proteins (MLH1, PMS2, MSH2, MSH6) using immunohistochemistry or MSI status using polymerase chain reaction (PCR), respectively. Results: MSI-H was detected in 19 (21.1%) patients. MSI-H was located more in ascending colon (36.8% vs. 9.9%, p-value = 0.0039) and less in sigmoid (5.3% vs. 33.8%, p-value = 0.0136) than MSS patients. Most patients were stage II for MSI-H (42.1%) as well as for MSS (56.3%), with significant more G1 (40.9% vs. 15.8%, p-value = 0.0427) for MSS patients. Gender, N stage, and M stage were identified as significant prognostic factors in multivariate analysis. MSI status was not a statistically significant predictor neither in univariate analysis nor multivariate analysis. Conclusion: Considering the efficacy of PD-1 inhibitor in metastatic CRC with MSI-H or dMMR, and its recent approval in EU, it is increasingly important to understand the prevalence across tumor stage, histology, and demographics, since our study displayed higher regional MSI-H prevalence (21%) compared to the literature. MDPI 2021-08-20 /pmc/articles/PMC8401048/ /pubmed/34441055 http://dx.doi.org/10.3390/medicina57080847 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lungulescu, Cristina
Croitoru, Vlad Mihai
Volovat, Simona Ruxandra
Cazacu, Irina Mihaela
Turcu-Stiolica, Adina
Gheonea, Dan Ionut
Sur, Daniel
Lungulescu, Cristian Virgil
An Insight into Deficient Mismatch Repair Colorectal Cancer Screening in a Romanian Population—A Bi-Institutional Pilot Study
title An Insight into Deficient Mismatch Repair Colorectal Cancer Screening in a Romanian Population—A Bi-Institutional Pilot Study
title_full An Insight into Deficient Mismatch Repair Colorectal Cancer Screening in a Romanian Population—A Bi-Institutional Pilot Study
title_fullStr An Insight into Deficient Mismatch Repair Colorectal Cancer Screening in a Romanian Population—A Bi-Institutional Pilot Study
title_full_unstemmed An Insight into Deficient Mismatch Repair Colorectal Cancer Screening in a Romanian Population—A Bi-Institutional Pilot Study
title_short An Insight into Deficient Mismatch Repair Colorectal Cancer Screening in a Romanian Population—A Bi-Institutional Pilot Study
title_sort insight into deficient mismatch repair colorectal cancer screening in a romanian population—a bi-institutional pilot study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401048/
https://www.ncbi.nlm.nih.gov/pubmed/34441055
http://dx.doi.org/10.3390/medicina57080847
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