Repositorio
Institucional

Schillaci, Roxana

Mercogliano, Maria F.#Inurrigarro, Gloria#De Martino, Mara#Venturutti, Leandro#Rivas, Martin A.#Cordo-Russo, Rosalia#Proietti, Cecilia J.#Fernandez, Elmer A.#Frahm, Isabel#Barchuk, Sabrina#Allemand, Daniel H.#Figurelli, Silvina#Deza, Ernesto Gil#Ares, Sandra#Gercovich, Felipe G.#Cortese, Eduardo#Amasino, Matias#Guzman, Pablo#Roa, Juan C.#Elizalde, Patricia V.

Invasive micropapillary carcinoma of the breast overexpresses MUC4 and is associated with poor outcome to adjuvant trastuzumab in HER2-positive breast cancer

BMC

BMC CANCER

en

Background: Invasive micropapillary carcinoma of the breast (IMPC) is a histological tumor variant that occurs with low frequency characterized by an inside-out formation of tumor clusters with a pseudopapillary arrangement. IMPC is an aggressive tumor with poor clinical outcome. In addition, this histological subtype usually expresses human epidermal growth factor receptor 2 (HER2) which also correlates with a more aggressive tumor. In this work we studied the clinical significance of IMPC in HER2-positive breast cancer patients treated with adjuvant trastuzumab. We also analyzed mucin 4 (MUC4) expression as a novel biomarker to identify IMPC. Methods: We retrospectively studied 86 HER2-positive breast cancer patients treated with trastuzumab and chemotherapy in the adjuvant setting. We explored the association of the IMPC component with clinicopathological parameters at diagnosis and its prognostic value. We compared MUC4 expression in IMPC with respect to other histological breast cancer subtypes by immunohistochemistry. Results: IMPC, either as a pure entity or associated with invasive ductal carcinoma (IDC), was present in 18.6% of HER2-positive cases. It was positively correlated with estrogen receptor expression and tumor size and inversely correlated with patient's age. Disease-free survival was significantly lower in patients with IMPC (hazard ratio = 2.6, 95%, confidence interval 1.1-6.1, P = 0.0340). MUC4, a glycoprotein associated with metastasis, was strongly expressed in all IMPC cases tested. IMPC appeared as the histological breast cancer subtype with the highest MUC4 expression compared to IDC, lobular and mucinous carcinoma. Conclusion: In HER2-positive breast cancer, the presence of IMPC should be carefully examined. As it is often not informed, because it is relatively difficult to identify or altogether overlooked, we propose MUC4 expression as a useful biomarker to highlight IMPC presence. Patients with MUC4-positive tumors with IMPC component should be more frequently monitored and/ or receive additional therapies.

Artículo original

This work was supported by IDB/PICT 2012-382 from the Agencia Nacional de Promocion Cientifica y Tecnologica, Argentina (ANPCyT), by a grant from the National Cancer Institute (Argentina) 2016-2017 and by a grant from Alberto J. Roemmers Foundation awarded to RS, a grant from CONICET 1819/03 from Oncomed-Reno, awarded to PVE and RS, National Cancer Instutute (Argentina) 2016-2017, PID 2012-066 and IDB/PICT 2012-668 from ANPCyT awarded to PVE, National Cancer Instutute (Argentina) 2016-2017, PIP 2012 059 from CONICET and IDB/PICT 2012 1017 from ANPCyT awarded to CJP. Universidad Catolica de Cordoba (BOD/2016 to EAF) Secretaria de Ciencia y Tecnologia-Universidad Nacional de Cordoba (30720150101719CB to EAF) and the Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET).

Este trabajo fue financiado por BID/PICT 2012-382 de la Agencia Nacional de Promoción Científica y Tecnológica, Argentina (ANPCyT), por una subvención del Instituto Nacional del Cáncer (Argentina) 2016-2017 y por una subvención de la Fundación Alberto J. Roemmers otorgada a RS, una subvención de CONICET 1819/03 de Oncomed-Reno, otorgada a PVE y RS, Instituto Nacional del Cáncer (Argentina) 2016-2017, PID 2012-066 y BID/PICT 2012-668 de ANPCyT otorgados a PVE, Instituto Nacional del Cáncer (Argentina) 2016-2017, PIP 2012 059 de CONICET y BID/PICT 2012 1017 de ANPCyT otorgados a CJP. Universidad Católica de Córdoba (BOD/2016 a EAF) Secretaría de Ciencia y Tecnología-Universidad Nacional de Córdoba (30720150101719CB a EAF) y el Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET).

10.1186/s12885-017-3897-x

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Invasive micropapillary carcinoma of the breast (IMPC)# HER2# Mucin 4 (MUC4)# Trastuzumab

http://dx.doi.org/10.1186/s12885-017-3897-x

Oncology

Carcinoma micropapilar invasivo de mama (IMPC)# HER2# mucina 4 (MUC4)# Trastuzumab

Oncología

Biotecnología Relacionada con la Salud

Patología

WOS:000419223800008

Invasive micropapillary carcinoma of the breast overexpresses MUC4 and is associated with poor outcome to adjuvant trastuzumab in HER2-positive breast cancer

Artículo original

version publicada

BMC

BMC CANCER

Oncología

en

ANPCyT IDB/PICT 2012-382#CONICET 1819/03#National Cancer Instutute PID 2012-066#ANPCyT IDB/PICT 2012-668#National Cancer Instutute PIP 2012 059#Universidad Catolica de Cordoba BOD/2016#Universidad Catolica de Cordoba 30720150101719CB

ANPCyT IDB/PICT 2012-382

National Cancer Institute (Argentina)

Alberto J. Roemmers Foundation

Oncomed-Reno CONICET 1819/03

CONICET PIP 2012 059

Universidad Catolica de Cordoba BOD/2016

Universidad Nacional de Cordoba 30720150101719CB

CONICET

ANPCyT PID 2012-066

ANPCyT IDB/PICT 2012-668

ANPCyT IDB/PICT 2012 1017

This work was supported by IDB/PICT 2012-382 from the Agencia Nacional de Promocion Cientifica y Tecnologica, Argentina (ANPCyT), by a grant from the National Cancer Institute (Argentina) 2016-2017 and by a grant from Alberto J. Roemmers Foundation awarded to RS, a grant from CONICET 1819/03 from Oncomed-Reno, awarded to PVE and RS, National Cancer Instutute (Argentina) 2016-2017, PID 2012-066 and IDB/PICT 2012-668 from ANPCyT awarded to PVE, National Cancer Instutute (Argentina) 2016-2017, PIP 2012 059 from CONICET and IDB/PICT 2012 1017 from ANPCyT awarded to CJP. Universidad Catolica de Cordoba (BOD/2016 to EAF) Secretaria de Ciencia y Tecnologia-Universidad Nacional de Cordoba (30720150101719CB to EAF) and the Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET).

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