Next Article in Journal
Proteasome 26S Subunit, non-ATPase 3 (PSMD3) Regulates Breast Cancer by Stabilizing HER2 from Degradation
Next Article in Special Issue
CHI3L1, NTRK2, 1p/19q and IDH Status Predicts Prognosis in Glioma
Previous Article in Journal
Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s Survival
Previous Article in Special Issue
Diagnostic and Prognostic Potential of AKR1B10 in Human Hepatocellular Carcinoma
Article Menu

Export Article

Open AccessArticle
Cancers 2019, 11(4), 526; https://doi.org/10.3390/cancers11040526

Automated Quantification of Extranuclear ERα using Phosphor-integrated Dots for Predicting Endocrine Therapy Resistance in HR+/HER2 Breast Cancer

1
Department of Breast and Endocrine Surgical Oncology, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8574, Japan
2
Department of Medical Physics, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8574, Japan
3
Department of Molecular and Functional Dynamics, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8574, Japan
4
Bio Systems Development Group, Bio Advanced Technology Division, Corporate R&D Headquarters, KONICA MINOLTA, INC., Hino, Tokyo 191-8511, Japan
*
Author to whom correspondence should be addressed.
Received: 2 March 2019 / Revised: 1 April 2019 / Accepted: 9 April 2019 / Published: 12 April 2019
(This article belongs to the Collection Cancer Biomarkers)
PDF [2515 KB, uploaded 12 April 2019]

Abstract

In addition to genomic signaling, Estrogen receptor alpha (ERα) is associated with cell proliferation and survival through extranuclear signaling contributing to endocrine therapy (ET) resistance. However, the relationship between extranuclear ERα and ET resistance has not been extensively studied. We sought to measure extranuclear ERα expression by immunohistochemistry using phosphor-integrated dots (IHC-PIDs) and to assess its predictive value for ET resistance. After quantitative detection of ERα by IHC-PIDs in vitro, we developed “the nearest-neighbor method” to calculate the extranuclear ERα. Furthermore, tissue sections from 65 patients with HR+/HER2- BC were examined by IHC-PIDs, and the total ERα, nuclear ERα, extranuclear ERα PIDs score, and ratio of extranuclear-to-nuclear ERα (ENR) were measured using the novel method. We demonstrate that quantification of ERα using IHC-PIDs exhibited strong correlations to real-time qRT-PCR (r2 = 0.94) and flow cytometry (r2 = 0.98). High ERα ENR was significantly associated with poor overall survival (p = 0.048) and disease-free survival (DFS) (p = 0.007). Multivariate analysis revealed that the ERα ENR was an independent prognostic factor for DFS [hazard ratio, 3.8; 95% CI, 1.4–11.8; p = 0.006]. Our automated measurement has high accuracy to localize and assess extranuclear ERα. A high ERα ENR in HR+/HER2 BC indicates decreased likelihood of benefiting from ET.
Keywords: breast cancer; estrogen receptor α; IHC-PIDs; prognostic; endocrine therapy resistance breast cancer; estrogen receptor α; IHC-PIDs; prognostic; endocrine therapy resistance
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Guo, Z.; Tada, H.; Kitamura, N.; Hamada, Y.; Miyashita, M.; Harada-Shoji, N.; Sato, A.; Hamanaka, Y.; Tsuboi, K.; Harada, N.; Takano-Kasuya, M.; Okada, H.; Nakano, Y.; Ohuchi, N.; Hayashi, S.-I.; Ishida, T.; Gonda, K. Automated Quantification of Extranuclear ERα using Phosphor-integrated Dots for Predicting Endocrine Therapy Resistance in HR+/HER2 Breast Cancer. Cancers 2019, 11, 526.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top