Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes

HER2+ breast cancer (BC) is an aggressive subtype representing a genetically and biologically heterogeneous group of tumors resulting in variable prognosis and treatment response to HER2-targeted therapies according to estrogen (ER) and progesterone receptor (PR) expression. The relationship with an...

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Main Authors: Sandra Orrù, Emanuele Pascariello, Giovanni Sotgiu, Daniela Piras, Laura Saderi, Maria Rosaria Muroni, Ciriaco Carru, Caterina Arru, Cristina Mocci, Giampietro Pinna, Raffaele Barbara, Paolo Cossu-Rocca, Maria Rosaria De Miglio
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Language:English
Published: MDPI AG 2022-01-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/10/1/164
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author Sandra Orrù
Emanuele Pascariello
Giovanni Sotgiu
Daniela Piras
Laura Saderi
Maria Rosaria Muroni
Ciriaco Carru
Caterina Arru
Cristina Mocci
Giampietro Pinna
Raffaele Barbara
Paolo Cossu-Rocca
Maria Rosaria De Miglio
author_facet Sandra Orrù
Emanuele Pascariello
Giovanni Sotgiu
Daniela Piras
Laura Saderi
Maria Rosaria Muroni
Ciriaco Carru
Caterina Arru
Cristina Mocci
Giampietro Pinna
Raffaele Barbara
Paolo Cossu-Rocca
Maria Rosaria De Miglio
author_sort Sandra Orrù
collection DOAJ
description HER2+ breast cancer (BC) is an aggressive subtype representing a genetically and biologically heterogeneous group of tumors resulting in variable prognosis and treatment response to HER2-targeted therapies according to estrogen (ER) and progesterone receptor (PR) expression. The relationship with androgen receptors (AR), a member of the steroid hormone’s family, is unwell known in BC. The present study aims to evaluate the prognostic impact of AR expression in HER2+ BC subtypes. A total of 695 BCs were selected and reviewed, AR, ER, PR and HER2 expression in tumor cells were examined by immunohistochemical method, and the SISH method was used in case of HER2 with equivocal immunohistochemical score (2+). A high prevalence of AR expression (91.5%) in BC HER+ was observed, with minimal differences between luminal and non-luminal tumor. According to steroid receptor expression, tumors were classified in four subgroups, including BC luminal and non-luminal HER2+ expressing or not AR. The luminal BC HER2 + AR+ was associated with lower histological grade, lower tumor size, higher PR expression and lower HER2 intensity of expression (2+). Also, the non-luminal tumors AR+ showed lower tumor size and lower prognostic stage but frequently higher grade and higher HER2 intensity of expression (3+). These findings should suggest a different progression of luminal and non-luminal tumors, both expressing AR, and allow us to speculate that the molecular mechanisms of AR, involved in the biology of BC HER2 + AR+, differ in relation to ER and PR expression. Moreover, AR expression may be a useful predictor of prognosis for overall survival (OS) in HER2+ BC subtypes. Our findings suggest that AR expression evaluation in clinical practice could be utilized in clinical oncology to establish different aggressiveness in BC HER2+ subtypes.
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spelling doaj.art-bf04c690ceb04924bd09c6ecb2d72a652023-11-23T13:04:53ZengMDPI AGBiomedicines2227-90592022-01-0110116410.3390/biomedicines10010164Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma SubtypesSandra Orrù0Emanuele Pascariello1Giovanni Sotgiu2Daniela Piras3Laura Saderi4Maria Rosaria Muroni5Ciriaco Carru6Caterina Arru7Cristina Mocci8Giampietro Pinna9Raffaele Barbara10Paolo Cossu-Rocca11Maria Rosaria De Miglio12Department of Pathology, “A. Businco” Oncologic Hospital, ARNAS Brotzu, Via Edward Jenner 1, 09121 Cagliari, ItalyDepartment of Pathology, “A. Businco” Oncologic Hospital, ARNAS Brotzu, Via Edward Jenner 1, 09121 Cagliari, ItalyDepartment of Medical, Surgical and Experimental Sciences, University of Sassari, Via P. Manzella 4, 07100 Sassari, ItalyStruttura Complessa Epidemiologia e Registro Tumori Nord Sardegna, ATS Sardegna, Via Rizzeddu 2, 07100 Sassari, ItalyDepartment of Medical, Surgical and Experimental Sciences, University of Sassari, Via P. Manzella 4, 07100 Sassari, ItalyDepartment of Medical, Surgical and Experimental Sciences, University of Sassari, Via P. Manzella 4, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, Viale San Pietro 43, 07100 Sassari, ItalyDepartment of Biomedical Sciences, University of Sassari, Viale San Pietro 43, 07100 Sassari, ItalyDepartment of Pathology, “A. Businco” Oncologic Hospital, ARNAS Brotzu, Via Edward Jenner 1, 09121 Cagliari, ItalyDepartment of Pathology, “A. Businco” Oncologic Hospital, ARNAS Brotzu, Via Edward Jenner 1, 09121 Cagliari, ItalyDepartment of Radiotherapy, “A. Businco” Oncologic Hospital, ARNAS Brotzu, Via Edward Jenner 1, 09121 Cagliari, ItalyDepartment of Medical, Surgical and Experimental Sciences, University of Sassari, Via P. Manzella 4, 07100 Sassari, ItalyDepartment of Medical, Surgical and Experimental Sciences, University of Sassari, Via P. Manzella 4, 07100 Sassari, ItalyHER2+ breast cancer (BC) is an aggressive subtype representing a genetically and biologically heterogeneous group of tumors resulting in variable prognosis and treatment response to HER2-targeted therapies according to estrogen (ER) and progesterone receptor (PR) expression. The relationship with androgen receptors (AR), a member of the steroid hormone’s family, is unwell known in BC. The present study aims to evaluate the prognostic impact of AR expression in HER2+ BC subtypes. A total of 695 BCs were selected and reviewed, AR, ER, PR and HER2 expression in tumor cells were examined by immunohistochemical method, and the SISH method was used in case of HER2 with equivocal immunohistochemical score (2+). A high prevalence of AR expression (91.5%) in BC HER+ was observed, with minimal differences between luminal and non-luminal tumor. According to steroid receptor expression, tumors were classified in four subgroups, including BC luminal and non-luminal HER2+ expressing or not AR. The luminal BC HER2 + AR+ was associated with lower histological grade, lower tumor size, higher PR expression and lower HER2 intensity of expression (2+). Also, the non-luminal tumors AR+ showed lower tumor size and lower prognostic stage but frequently higher grade and higher HER2 intensity of expression (3+). These findings should suggest a different progression of luminal and non-luminal tumors, both expressing AR, and allow us to speculate that the molecular mechanisms of AR, involved in the biology of BC HER2 + AR+, differ in relation to ER and PR expression. Moreover, AR expression may be a useful predictor of prognosis for overall survival (OS) in HER2+ BC subtypes. Our findings suggest that AR expression evaluation in clinical practice could be utilized in clinical oncology to establish different aggressiveness in BC HER2+ subtypes.https://www.mdpi.com/2227-9059/10/1/164HER2 expressionAR expressionbreast cancerprognosisimmunohistochemistry
spellingShingle Sandra Orrù
Emanuele Pascariello
Giovanni Sotgiu
Daniela Piras
Laura Saderi
Maria Rosaria Muroni
Ciriaco Carru
Caterina Arru
Cristina Mocci
Giampietro Pinna
Raffaele Barbara
Paolo Cossu-Rocca
Maria Rosaria De Miglio
Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes
Biomedicines
HER2 expression
AR expression
breast cancer
prognosis
immunohistochemistry
title Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes
title_full Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes
title_fullStr Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes
title_full_unstemmed Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes
title_short Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes
title_sort prognostic role of androgen receptor expression in her2 breast carcinoma subtypes
topic HER2 expression
AR expression
breast cancer
prognosis
immunohistochemistry
url https://www.mdpi.com/2227-9059/10/1/164
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