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Rev Bras Ginecol Obstet 2016; 38(06): 280-286
DOI: 10.1055/s-0036-1584954
Original Article
Thieme Publicações Ltda Rio de Janeiro, Brazil

EZH2 Protein Expression and Tumor Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

Expressão da proteína EZH2 e resposta tumoral à quimioterapia neoadjuvante no câncer de mama localmente avançado
Lucienne Pereira Del Grossi Neusquen
1   Department of Obstetrics and Gynecology, Universidade de São Paulo, São Paulo, São Paulo, Brazil
,
José Roberto Filassi
1   Department of Obstetrics and Gynecology, Universidade de São Paulo, São Paulo, São Paulo, Brazil
,
Carlos Elias Fristachi
2   Instituto Arnaldo Vieira de Carvalho, São Paulo, São Paulo, Brazil
,
Kátia Candido Carvalho
3   Laboratory of Structural and Molecular Gynecology (LIM-58), Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil
,
Maíra Teixeira Dória
1   Department of Obstetrics and Gynecology, Universidade de São Paulo, São Paulo, São Paulo, Brazil
,
José Maria Soares Júnior
1   Department of Obstetrics and Gynecology, Universidade de São Paulo, São Paulo, São Paulo, Brazil
3   Laboratory of Structural and Molecular Gynecology (LIM-58), Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil
,
José Roberto Morales Piato
1   Department of Obstetrics and Gynecology, Universidade de São Paulo, São Paulo, São Paulo, Brazil
› Author Affiliations
Further Information

Publication History

23 January 2016

18 May 2016

Publication Date:
11 July 2016 (online)

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Abstract

Introduction Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced breast cancer. However, some tumors will not respond to this treatment due to histological and molecular features. The protein EZH2 (enhancer of zest homolog 2) is a histone methyltransferase that is correlated with poorly differentiated breast carcinomas and aggressive tumor behavior.

Purpose The present study evaluated the association between EZH2 expression and response to NAC, and its correlation with HER2 overexpression, estrogen and progesterone receptors (ER, PR) and Ki-67 proliferation index.

Methods A total of 60 patients with locally advanced breast cancer treated with NAC were selected for this study. Twenty-three paraffin blocks had not enough material for tissue resection, and were not evaluated. A tissue microarray based in immunohistochemistry (IHC) analysis of EZH2 was performed for the remaining 37 specimens. Patients were divided into two groups based on response to NAC.

Results EZH2 expression was significantly associated with markers of poor prognosis such as ER negativity (p = 0.001), PR negativity (p = 0.042) and high Ki-67 proliferation index (p = 0.002). High EZH2 expression was not correlated with the response to NAC.

Conclusions Our data suggested that EZH2 protein expression may not correlate with the clinical response to NAC. Other studies with more patients are needed to confirm this observation.

Resumo

Introdução A quimioterapia neoadjuvante é o tratamento padrão para os cânceres de mama localmente avançados. Entretanto, apenas uma porcentagem desses tumores irá responder ao tratamento, devido a características histológicas e moleculares. A proteína EZH2 (enhancer of zest homolog 2) é uma histona metiltransferase associada a tumores mal diferenciados e de comportamento agressivo.

Objetivo O presente estudo teve como objetivo avaliar a associação entre a expressão da proteína EZH2 e a resposta à quimioterapia neoadjuvante, além da correlação dessa proteína com hiper-expressão de HER2, receptores de estrogênio e progesterona, e o marcador de proliferação Ki-67.

Métodos Um total de 60 pacientes com câncer de mama localmente avançado tratadas com quimioterapia neoadjuvante foram selecionadas para esse estudo. Vinte e três blocos de parafina não continham material suficiente para ressecção e não foram avaliados. Foi realizado microarray baseado em análise imuno-histoquímica da proteína EZH2 para as 36 pacientes restantes. As pacientes foram divididas em dois grupos baseado na resposta à quimioterapia neoadjuvante.

Resultados A expressão da proteína EZH2 foi significativamente associada com marcadores de pior prognóstico, como negatividade para receptor de estrogênio (p = 0,001) e progesterona (p = 0,042), além de alto Ki-67 (p = 0,002). Entretanto, a alta expressão da EZH2 não se correlacionou com a resposta à quimioterapia neoadjuvante.

Conclusões Nossos dados sugerem que a expressão da proteína EZH2 pode não estar relacionada com a resposta clínica à quimioterapia neoadjuvante. Outros estudos com maior número de pacientes são necessários para confirmar esses achados.

Keywords

EZH2 - breast neoplasms - tumor markers - neoadjuvant therapy - gene expression

Palavras-chave

EZH2 - neoplasias da mama - marcadores tumorais - terapia neoadjuvante - expressão gênica
 

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