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

Autor:	Akiko Sato, Minoru Miyashita, Nobuhisa Harada, Kouki Tsuboi, Hisatake Okada, Yoh Hamada, Mayumi Takano-Kasuya, Zhaorong Guo, Narufumi Kitamura, Narumi Harada-Shoji, Takanori Ishida, Yasushi Nakano, Shin Ichi Hayashi, Yohei Hamanaka, Noriaki Ohuchi, Kohsuke Gonda, Hiroshi Tada
Rok vydání:	2019
Předmět:	0301 basic medicine IHC-PIDs Cancer Research lcsh:RC254-282 Flow cytometry 03 medical and health sciences breast cancer 0302 clinical medicine Breast cancer medicine medicine.diagnostic_test Cell growth Chemistry endocrine therapy resistance Endocrine therapy estrogen receptor α lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease In vitro 030104 developmental biology Tissue sections Oncology 030220 oncology & carcinogenesis Cancer research Immunohistochemistry prognostic Estrogen receptor alpha hormones hormone substitutes and hormone antagonists
Zdroj:	Cancers, Vol 11, Iss 4, p 526 (2019) Cancers Volume 11 Issue 4
ISSN:	2072-6694
DOI:	10.3390/cancers11040526
Popis:	In addition to genomic signaling, Estrogen receptor alpha (ER&alpha ) is associated with cell proliferation and survival through extranuclear signaling contributing to endocrine therapy (ET) resistance. However, the relationship between extranuclear ER&alpha and ET resistance has not been extensively studied. We sought to measure extranuclear ER&alpha expression by immunohistochemistry using phosphor-integrated dots (IHC-PIDs) and to assess its predictive value for ET resistance. After quantitative detection of ER&alpha by IHC-PIDs in vitro, we developed &ldquo the nearest-neighbor method&rdquo to calculate the extranuclear ER&alpha Furthermore, tissue sections from 65 patients with HR+/HER2- BC were examined by IHC-PIDs, and the total ER&alpha nuclear ER&alpha extranuclear ER&alpha PIDs score, and ratio of extranuclear-to-nuclear ER&alpha (ENR) were measured using the novel method. We demonstrate that quantification of ER&alpha using IHC-PIDs exhibited strong correlations to real-time qRT-PCR (r2 = 0.94) and flow cytometry (r2 = 0.98). High ER&alpha ENR was significantly associated with poor overall survival (p = 0.048) and disease-free survival (DFS) (p = 0.007). Multivariate analysis revealed that the ER&alpha ENR was an independent prognostic factor for DFS [hazard ratio, 3.8 95% CI, 1.4&ndash 11.8 p = 0.006]. Our automated measurement has high accuracy to localize and assess extranuclear ER&alpha A high ER&alpha ENR in HR+/HER2&minus BC indicates decreased likelihood of benefiting from ET.
Databáze:	OpenAIRE
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