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J Pathol ; 246(3): 379-389, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30058236

RESUMO

Human epidermal growth factor receptor 2 (HER2) is a target of the HER2 inhibitor trastuzumab, which has been administered to HER2-positive breast cancer patients. However, the therapeutic effects of HER2 inhibitor monotherapy are not always clinically effective as compared with cotreatment with chemotherapy. Therefore, it has become pivotal to predict the therapeutic efficacy of trastuzumab monotherapy prior to administration. Recently, carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) has been reported to be a HER2-related factor. The aim of the present study was to explore the therapeutic mechanism of trastuzumab, including the relevance of CEACAM6 expression. CEACAM6/HER2-double-positive human breast carcinoma cell lines BT-474, HCC-1419 and MDA-MB-361 were used in this study. CEACAM6 knockdown decreased the inhibitory effects of trastuzumab in the trastuzumab-sensitive BT-474 and HCC-1419 cells, but not in the trastuzumab-resistant MDA-MB-361 cells. We examined the interaction between CEACAM6 and HER2 by using a proximity ligation assay (PLA). The interaction was detected in BT-474 and HCC-1419 cells, but not in MDA-MB-361 cells, and was significantly associated with in vitro trastuzumab therapeutic sensitivity. We further analysed the status of CEACAM6 and HER2 and their interaction in archival pathology specimens, also using PLA. The interaction was detected only in CEACAM6/HER2-double-positive breast cancer cases, and their PLA score was significantly associated with the efficacy of trastuzumab treatment. Therefore, evaluation of the CEACAM6-HER2 interaction could serve as a marker to predict the efficacy of trastuzumab monotherapy in breast cancer patients. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Antígenos CD/metabolismo , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Moléculas de Adesão Celular/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quimioterapia Adjuvante , Resistencia a Medicamentos Antineoplásicos , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Ligação Proteica , Receptor ErbB-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
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