Wild-type oestrogen receptor beta (ERβ1) mRNA and protein expression in Tamoxifen-treated post-menopausal breast cancers

Abstract

This study has tested the hypothesis that comparison of protein and mRNA expression for ERa and ERb1 by human breast cancers provides novel information relating to the clinical and pathological characteristics of human breast cancers. Expression of ERa and ERb1 was identified in 167 invasive cancers from postmenopausal women treated only with endocrine therapy. The cohort included 143 cases receiving only adjuvant Tamoxifen following surgery. ERa and ERb1 expression was analysed by immunohistochemistry and reverse transcription RT -PCR and compared with clinical progression of individual cancers. ERa protein was closely associated with the corresponding RNA detected by RT -PCR (Chi-square, Po0.001). In contrast, ERb1 protein and mRNA were inconsistent. Although an association was identified between ERa and ERb mRNAs (Chi-square, Po0.001) and between ERa protein and ERb1 mRNA (Chi-square, Po0.027), no association was identified for the ERa and ERb1 proteins detected by immunohistochemistry. ERb1 was not associated with outcome. However, in the absence of ERa, ERb1 protein expression was associated with elevated cell proliferation. There was a trend for the ERb1 protein-positive cases to have a worse outcome, both within the group as a whole as well as within the ERa-positive Tamoxifen-treated cases. This study has confirmed the hypothesis that expression of ERa is an important determinant of breast cancer progression, and has further demonstrated that ERb1 may play a role in the response of breast cancers to endocrine therapy.

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

“…Moreover, loss of ERb was observed to be associated with tamoxifen resistance whereas increase of ERb expression in MCF-7 cells enhanced the antiproliferative and apoptotic effect of antiestrogens (HodgesGallagher et al, 2008). However, data regarding the association of ERb expression with clinical pathological parameters and antiestrogen responsiveness are still mixed (Speirs et al, 1999;O'Neill et al, 2004;Murphy and Watson, 2006).…”

ERβ in breast cancer—Onlooker, passive player, or active protector?

“…The region of the mRNA targeted by primers may also influence which variants are detected. Several investigators have reported that ERβ mRNA levels often do not correlate with ERβ protein in breast tumor tissues [80][81][82][83][84], and confusion with ERβ status in tumors may result from this method. If fact, in one report only 54% of ERβ mRNA-positive tumors correlated with ERβ protein levels [84].…”

“…Both antibody types have been used; however, sample preparation and integrity as well as specific staining protocols may influence outcomes [79]. With variation in the choice of ERβ antibody and tissue fixation protocols, there is not yet firm agreement on the appropriate cutoff value for determining ERβ positivity [78,82].…”

“…In general, ERα protein expression correlates with low tumor grade and negative lymph node status, and ERα+ tumors are associated with better DFS and OS [63,81,82]. ERα+ tumors are usually less invasive and have a more favorable prognosis [100].…”

“…However, the correlation between ERβ expression and invasiveness is less clear. Although numerous researchers found no significant correlation between ERβ protein expression and tumor grade [81,82,88,90,95,97,98,[101][102][103][104], several groups showed that ERβ expression significantly correlates with low tumor grade [63,80,105] or in one case higher histological grade [89]. In these studies, all ERβ-containing tumors were analyzed together and included ERα+/ERβ+ (the majority) as well as ERα−/ERβ+ tumors.…”