Wild-type oestrogen receptor beta (ERbeta1) mRNA and protein expression in Tamoxifen-treated post-menopausal breast cancers.
This study has tested the hypothesis that comparison of protein and mRNA expression for ERalpha and ERbeta1 by human breast cancers provides novel information relating to the clinical and pathological characteristics of human breast cancers. Expression of ERalpha and ERbeta1 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. ERalpha and ERbeta1 expression was analysed by immunohistochemistry and reverse transcription RT-PCR and compared with clinical progression of individual cancers. ERalpha protein was closely associated with the corresponding RNA detected by RT-PCR (Chi-square, P<0.001). In contrast, ERbeta1 protein and mRNA were inconsistent. Although an association was identified between ERalpha and ERbeta mRNAs (Chi-square, P<0.001) and between ERalpha protein and ERbeta1 mRNA (Chi-square, P<0.027), no association was identified for the ERalpha and ERbeta1 proteins detected by immunohistochemistry. ERbeta1 was not associated with outcome. However, in the absence of ERalpha, ERbeta1 protein expression was associated with elevated cell proliferation. There was a trend for the ERbeta1 protein-positive cases to have a worse outcome, both within the group as a whole as well as within the ERalpha-positive Tamoxifen-treated cases. This study has confirmed the hypothesis that expression of ERalpha is an important determinant of breast cancer progression, and has further demonstrated that ERbeta1 may play a role in the response of breast cancers to endocrine therapy.
O'Neill
P A
PA
Clatterbridge Cancer Research Trust, J.K. Douglas Laboratories, Clatterbridge Hospital, Bebington, Wirral, CH63 4JY, UK.
Davies
M P A
MP
Shaaban
A M
AM
Innes
H
H
Torevell
A
A
Sibson
D R
DR
Foster
C S
CS
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D012333:RNA, Messenger / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011980:Receptors, Progesterone; D013629:Tamoxifen