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Differences in the Molecular Profile between Primary Breast Carcinomas and Their Cutaneous Metastases

SIMPLE SUMMARY: The development of new strategies for the management of cutaneous metastases is a major clinical challenge because of the poor prognosis. To advance in this field, a better understanding of the molecular alterations involved in the metastatic process is needed. In the present study,...

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Autores principales: González-Martínez, Silvia, Pizarro, David, Pérez-Mies, Belén, Caniego-Casas, Tamara, Rodríguez-Peralto, José Luis, Curigliano, Giuseppe, Cortés, Alfonso, Gión, María, Cortés, Javier, Palacios, José
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909188/
https://www.ncbi.nlm.nih.gov/pubmed/35267459
http://dx.doi.org/10.3390/cancers14051151
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author González-Martínez, Silvia
Pizarro, David
Pérez-Mies, Belén
Caniego-Casas, Tamara
Rodríguez-Peralto, José Luis
Curigliano, Giuseppe
Cortés, Alfonso
Gión, María
Cortés, Javier
Palacios, José
author_facet González-Martínez, Silvia
Pizarro, David
Pérez-Mies, Belén
Caniego-Casas, Tamara
Rodríguez-Peralto, José Luis
Curigliano, Giuseppe
Cortés, Alfonso
Gión, María
Cortés, Javier
Palacios, José
author_sort González-Martínez, Silvia
collection PubMed
description SIMPLE SUMMARY: The development of new strategies for the management of cutaneous metastases is a major clinical challenge because of the poor prognosis. To advance in this field, a better understanding of the molecular alterations involved in the metastatic process is needed. In the present study, the clinicopathological characteristics of breast cancer that develop cutaneous metastases were analyzed and the molecular differences between primary breast tumors and their corresponding cutaneous metastases were compared. We observed that the surrogate molecular type of breast cancer with an increased risk to metastasize to the skin was triple negative. In total, 48.5% of the cutaneous metastases presented some additional molecular alteration with respect to the primary tumor. However, no characteristic mutational pattern related to skin metastasis development was observed. Identifying the genes involved in the development of cutaneous metastases is important to gain insights into the biology of the disease and to identify possible diagnostic and therapeutic biomarkers. ABSTRACT: Background: The characterization of molecular alterations of primary breast carcinomas (BC) and their cutaneous metastases (CM) to identify genes involved in the metastatic process have not yet been completely accomplished. Methods: To investigate the molecular alterations of BC and their CM, a total of 66 samples (33 BC and 33 CM) from 33 patients were analyzed by immunohistochemical and massive parallel sequencing analyses. In addition, the clinicopathological characteristics of patients and tumors were analyzed. Results: Triple negative (TN) BCs were overrepresented (36.4%) among tumors that developed CM. A change of tumor surrogate molecular type in metastases was found in 15% of patients and 48.5% of the CM presented some additional molecular alteration with respect to the primary tumor, the most frequent were amplification of MYC and MDM4, and mutations in TP53 and PIK3CA. Survival was related to histological grade, tumor surrogate molecular type and TP53 mutations in the univariate analysis but only the tumor surrogate molecular type remained as a prognostic factor in the multivariate analysis. Conclusions: The TN molecular type has a greater risk of developing skin metastases. There are phenotypic changes and additional molecular alterations in skin metastases compared to the corresponding primary breast tumors in nearly half of the patients. Although these changes do not follow a specific pattern and varied from patient to patient, they could impact on the treatment. More studies with larger patient and sample cohorts are needed.
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spelling pubmed-89091882022-03-11 Differences in the Molecular Profile between Primary Breast Carcinomas and Their Cutaneous Metastases González-Martínez, Silvia Pizarro, David Pérez-Mies, Belén Caniego-Casas, Tamara Rodríguez-Peralto, José Luis Curigliano, Giuseppe Cortés, Alfonso Gión, María Cortés, Javier Palacios, José Cancers (Basel) Article SIMPLE SUMMARY: The development of new strategies for the management of cutaneous metastases is a major clinical challenge because of the poor prognosis. To advance in this field, a better understanding of the molecular alterations involved in the metastatic process is needed. In the present study, the clinicopathological characteristics of breast cancer that develop cutaneous metastases were analyzed and the molecular differences between primary breast tumors and their corresponding cutaneous metastases were compared. We observed that the surrogate molecular type of breast cancer with an increased risk to metastasize to the skin was triple negative. In total, 48.5% of the cutaneous metastases presented some additional molecular alteration with respect to the primary tumor. However, no characteristic mutational pattern related to skin metastasis development was observed. Identifying the genes involved in the development of cutaneous metastases is important to gain insights into the biology of the disease and to identify possible diagnostic and therapeutic biomarkers. ABSTRACT: Background: The characterization of molecular alterations of primary breast carcinomas (BC) and their cutaneous metastases (CM) to identify genes involved in the metastatic process have not yet been completely accomplished. Methods: To investigate the molecular alterations of BC and their CM, a total of 66 samples (33 BC and 33 CM) from 33 patients were analyzed by immunohistochemical and massive parallel sequencing analyses. In addition, the clinicopathological characteristics of patients and tumors were analyzed. Results: Triple negative (TN) BCs were overrepresented (36.4%) among tumors that developed CM. A change of tumor surrogate molecular type in metastases was found in 15% of patients and 48.5% of the CM presented some additional molecular alteration with respect to the primary tumor, the most frequent were amplification of MYC and MDM4, and mutations in TP53 and PIK3CA. Survival was related to histological grade, tumor surrogate molecular type and TP53 mutations in the univariate analysis but only the tumor surrogate molecular type remained as a prognostic factor in the multivariate analysis. Conclusions: The TN molecular type has a greater risk of developing skin metastases. There are phenotypic changes and additional molecular alterations in skin metastases compared to the corresponding primary breast tumors in nearly half of the patients. Although these changes do not follow a specific pattern and varied from patient to patient, they could impact on the treatment. More studies with larger patient and sample cohorts are needed. MDPI 2022-02-23 /pmc/articles/PMC8909188/ /pubmed/35267459 http://dx.doi.org/10.3390/cancers14051151 Text en © 2022 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
González-Martínez, Silvia
Pizarro, David
Pérez-Mies, Belén
Caniego-Casas, Tamara
Rodríguez-Peralto, José Luis
Curigliano, Giuseppe
Cortés, Alfonso
Gión, María
Cortés, Javier
Palacios, José
Differences in the Molecular Profile between Primary Breast Carcinomas and Their Cutaneous Metastases
title Differences in the Molecular Profile between Primary Breast Carcinomas and Their Cutaneous Metastases
title_full Differences in the Molecular Profile between Primary Breast Carcinomas and Their Cutaneous Metastases
title_fullStr Differences in the Molecular Profile between Primary Breast Carcinomas and Their Cutaneous Metastases
title_full_unstemmed Differences in the Molecular Profile between Primary Breast Carcinomas and Their Cutaneous Metastases
title_short Differences in the Molecular Profile between Primary Breast Carcinomas and Their Cutaneous Metastases
title_sort differences in the molecular profile between primary breast carcinomas and their cutaneous metastases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909188/
https://www.ncbi.nlm.nih.gov/pubmed/35267459
http://dx.doi.org/10.3390/cancers14051151
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