Open AccessIndividual transcriptional activity of estrogen receptors in primary breast cancer and its clinical significance
Author(s) -
Gohno Tatsuyuki,
Seino Yuko,
Hanamura Toru,
Niwa Toshifumi,
Matsumoto Mitsuyo,
Yaegashi Nobuo,
Oba Hanako,
Kurosumi Masafumi,
Takei Hiroyuki,
Yamaguchi Yuri,
Hayashi Shinichi
Publication year - 2012
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.41
Subject(s) - estrogen receptor , breast cancer , estrogen , messenger rna , immunohistochemistry , malignancy , estrogen receptor alpha , biology , cancer research , cancer , biomarker , progesterone receptor , estrogen receptor beta , gene expression , medicine , gene , endocrinology , genetics
To predict the efficacy of hormonal therapy at the individual‐level, immunohistochemical methods are used to analyze expression of classical molecular biomarkers such as estrogen receptor ( ER ), progesterone receptor ( PgR ), and HER2 . However, the current diagnostic standard is not perfect for the individualization of diverse cases. Therefore, establishment of more accurate diagnostics is required. Previously, we established a novel method that enables analysis of ER transcriptional activation potential in clinical specimens using an adenovirus estrogen response element–green fluorescence protein ( ERE ‐ GFP ) assay system. Using this assay, we assessed the ERE transcriptional activity of 62 primary breast cancer samples. In 40% of samples, we observed that ER protein expression was not consistent with ERE activity. Comparison of ERE activity with clinicopathological information revealed that ERE activity was significantly correlated with the ER target gene, PgR , rather than ER in terms of both protein and mRNA expression. Moreover, subgrouping of L uminal A ‐type breast cancer samples according to ERE activity revealed that ER α mRNA expression correlated with ER target gene mRNA expression in the high‐, but not the low‐, ERE ‐activity group. On the other hand, the low‐ ERE ‐activity group showed significantly higher mRNA expression of the malignancy biomarker Ki67 in association with disease recurrence in 5% of patients. Thus, these data suggest that ER expression does not always correlate with ER transcriptional activity. Therefore, in addition to ER protein expression, determination of ERE activity as an ER functional marker will be helpful for analysis of a variety of diverse breast cancer cases and the subsequent course of treatment.