- Paper Report
- Open Access
ER variants in breast cancer
- Valerie Speirs1
© Current Science Ltd 2000
- Published: 1 December 2000
- Breast cancer
- estrogen receptor variants
ER is expressed in approximately 60% of all breast cancers. It is an independent prognostic factor upon which decisions on whether to give hormonal therapy are based. Two forms of ER are known to exist, the original ER, now renamed ERα, and the more recently discovered, ERβ. The ERα gene consists of eight exons from which splice variants can arise due to alternative processing. The relative frequency of such variants in breast cancer progression is, however, unclear.
To identify the frequency of occurrence of variant forms of ERα mRNA in breast cancer.
Breast tumour samples (n = 110) and normal breast samples (n = 8) were used. Wild type ERα was determined by routine immunohistochemistry. cDNA was synthesised from total RNA and amplified by PCR using primers designed to detect specific regions of ERα. PCR products were cloned and sequenced using standard methods.
Sequence analysis of PCR-amplified cDNAs confirmed the absence of point mutations or small deletions in both normal breast and tumour samples. Although most samples contained ERα variants at low levels, only two out of 118 samples, both ductal carcinomas, showed variant ERs comparable to the intensity of the full size product when amplified using primers located in exons 6 and 8. One tumour expressed a single variant form, which was node positive but wild type ERα was undetectable by immunohistochemistry or northern blot. The second sample, of unknown node status, showed normal wild-type ERα by immunohistochemistry and northern blot and contained at least five ERα variants. Four out of five were processing variants and three had not previously been described. The main variant contained deletions in exons 2-5.
ERα variants occured at relatively low frequency in the panel of 118 breast tumours examined. This result suggests such variants play no major part in the development and progression of human breast cancer.
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