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MCM6 versus Ki-67 in diagnosis of luminal molecular subtypes of breast cancers

BACKGROUND: Currently, breast cancers are divided into four major molecular subtypes. The distinction between the luminal A and luminal B subtypes is mainly based on the cellular proliferation indices and is assessed by the Ki-67 scoring. Due to the limitations in the assessment and expression of Ki...

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Autores principales: Sadeghian, Dorsay, Saffar, Hana, Mahdavi Sharif, Pouya, Soleimani, Vahid, Jahanbin, Behnaz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818166/
https://www.ncbi.nlm.nih.gov/pubmed/35125121
http://dx.doi.org/10.1186/s13000-022-01209-4
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author Sadeghian, Dorsay
Saffar, Hana
Mahdavi Sharif, Pouya
Soleimani, Vahid
Jahanbin, Behnaz
author_facet Sadeghian, Dorsay
Saffar, Hana
Mahdavi Sharif, Pouya
Soleimani, Vahid
Jahanbin, Behnaz
author_sort Sadeghian, Dorsay
collection PubMed
description BACKGROUND: Currently, breast cancers are divided into four major molecular subtypes. The distinction between the luminal A and luminal B subtypes is mainly based on the cellular proliferation indices and is assessed by the Ki-67 scoring. Due to the limitations in the assessment and expression of Ki-67, we hypothesized that minichromosome maintenance protein 6 (MCM6) might be taken as a surrogate marker to differentiate molecular subtypes and aid in more precise grading of tumors. METHODS: We performed a retrospective, cross-sectional study on 124 samples of breast cancer and 40 samples of normal breast tissue. Relevant clinical information was retrieved from the Cancer Institute database. RESULTS: MCM6 could discriminate between various categories of histologic grades, tubule formation, mitotic indices, and nuclear pleomorphism (P = 0.002 for tubule formation and P < 0.001 for other). Moreover, the MCM6 score exhibited a significant correlation with the mitotic count (P < 0.001). However, the Ki-67 score could not discriminate subgroups of the mitotic index and nuclear pleomorphism. Compared to the luminal A subtype, luminal B exhibited a higher MCM6 score (P = 0.01). Besides, MCM6 scores were higher for certain subtypes with more aggressive behaviors, such as hormone receptor (HR)-negative disease, and human epidermal growth factor receptor 2 (HER2)-enriched and triple-negative breast cancers, as there was a significantly higher MCM6 mean score in the HR-negative in comparison to the luminal breast cancers (P < 0.001). Similarly, higher MCM6 scores were observed among samples with more advanced nuclear grades, tubule formation, and overall grades. CONCLUSION: MCM6 can differentiate luminal A and luminal B subtypes and is correlated with mitotic counts. However, this study was unable to prove the superiority of MCM6 in differentiating between molecular subtypes compared to the Ki-67 score. Nevertheless, in our study, MCM6 was superior to Ki-67 in exhibiting correlations with the mitotic grade, tubule formation, and nuclear grades. More studies are needed to standardize its assessment methods, determine more robust cut-off values, and evaluate its associations with prognostic features of breast cancer.
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spelling pubmed-88181662022-02-07 MCM6 versus Ki-67 in diagnosis of luminal molecular subtypes of breast cancers Sadeghian, Dorsay Saffar, Hana Mahdavi Sharif, Pouya Soleimani, Vahid Jahanbin, Behnaz Diagn Pathol Research BACKGROUND: Currently, breast cancers are divided into four major molecular subtypes. The distinction between the luminal A and luminal B subtypes is mainly based on the cellular proliferation indices and is assessed by the Ki-67 scoring. Due to the limitations in the assessment and expression of Ki-67, we hypothesized that minichromosome maintenance protein 6 (MCM6) might be taken as a surrogate marker to differentiate molecular subtypes and aid in more precise grading of tumors. METHODS: We performed a retrospective, cross-sectional study on 124 samples of breast cancer and 40 samples of normal breast tissue. Relevant clinical information was retrieved from the Cancer Institute database. RESULTS: MCM6 could discriminate between various categories of histologic grades, tubule formation, mitotic indices, and nuclear pleomorphism (P = 0.002 for tubule formation and P < 0.001 for other). Moreover, the MCM6 score exhibited a significant correlation with the mitotic count (P < 0.001). However, the Ki-67 score could not discriminate subgroups of the mitotic index and nuclear pleomorphism. Compared to the luminal A subtype, luminal B exhibited a higher MCM6 score (P = 0.01). Besides, MCM6 scores were higher for certain subtypes with more aggressive behaviors, such as hormone receptor (HR)-negative disease, and human epidermal growth factor receptor 2 (HER2)-enriched and triple-negative breast cancers, as there was a significantly higher MCM6 mean score in the HR-negative in comparison to the luminal breast cancers (P < 0.001). Similarly, higher MCM6 scores were observed among samples with more advanced nuclear grades, tubule formation, and overall grades. CONCLUSION: MCM6 can differentiate luminal A and luminal B subtypes and is correlated with mitotic counts. However, this study was unable to prove the superiority of MCM6 in differentiating between molecular subtypes compared to the Ki-67 score. Nevertheless, in our study, MCM6 was superior to Ki-67 in exhibiting correlations with the mitotic grade, tubule formation, and nuclear grades. More studies are needed to standardize its assessment methods, determine more robust cut-off values, and evaluate its associations with prognostic features of breast cancer. BioMed Central 2022-02-06 /pmc/articles/PMC8818166/ /pubmed/35125121 http://dx.doi.org/10.1186/s13000-022-01209-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Sadeghian, Dorsay
Saffar, Hana
Mahdavi Sharif, Pouya
Soleimani, Vahid
Jahanbin, Behnaz
MCM6 versus Ki-67 in diagnosis of luminal molecular subtypes of breast cancers
title MCM6 versus Ki-67 in diagnosis of luminal molecular subtypes of breast cancers
title_full MCM6 versus Ki-67 in diagnosis of luminal molecular subtypes of breast cancers
title_fullStr MCM6 versus Ki-67 in diagnosis of luminal molecular subtypes of breast cancers
title_full_unstemmed MCM6 versus Ki-67 in diagnosis of luminal molecular subtypes of breast cancers
title_short MCM6 versus Ki-67 in diagnosis of luminal molecular subtypes of breast cancers
title_sort mcm6 versus ki-67 in diagnosis of luminal molecular subtypes of breast cancers
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818166/
https://www.ncbi.nlm.nih.gov/pubmed/35125121
http://dx.doi.org/10.1186/s13000-022-01209-4
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