Oestrogen receptor beta: how should we measure this?

Sir

Since a second oestrogen receptor (ER), ERβ was identified in the middle of the 1990s (Mosselman ), there has been much effort directed into trying to define its biological role in hormone sensitive tissue such as the mammary gland, particularly at the protein level. In a recent issue of British Journal of Cancer, Saunders reported immunohistochemical detection of ERβ in 51 breast tumours. In their study cohort, almost all samples were positive for ERβ (48 out of 51; 94%). In an earlier issue of British Journal of Cancer (Skliris ), we too reported immunohistochemical detection of ERβ in a similar sized cohort of 63 breast tumours, and showed much less positive nuclear ERβ immunoreactivity (48 out of 65; 74%). It is interesting to note that both studies used an identical scoring system, based on assessing both staining intensity (scored 0–3) and percentage positivity (scored 0–5), which generates a numerical score ranging from 0–8 (Allred ). In both instances, a score of >2 was considered positive.

Why such divergent results in such similar sized cohorts? A Scottish–English patient bias seems unlikely (but has not been excluded!). However, it may be pertinent that each study used monoclonal antibodies directed against different parts of ERβ. More recent work from our group has shown a considerable variation in the efficacy of distinct ERβ antibodies to detect receptor protein under different applications (Skliris ) and Saunders also makes this point in her penultimate paragraph, when referring to other published immunohistochemical studies. It is also perhaps important to remind ourselves that the appropriate threshold for scoring a tumour as ‘positive’ for ERβ will remain unclear until immunohistochemical expression can be correlated with endocrine response in the clinical context. ERβ may well be an important player in the ER signalling cascade but until there is a recognised consensus on the best way to measure it in a clinically meaningful way, the waters will surely remain muddied.