Reliability of immunohistochemical demonstration of oestrogen receptors inroutine practice: interlaboratory variance in the sensitivity of detectionand evaluation of scoring systems

Aims-To investigate interlaboratory variance in the immunohistochemical (IH C) detection of oestrogen receptors so as to determine the rate of false ne gatives, which could adversely influence the decision to give adjuvant tam oxifen treatment. Methods-To ensure that similar results are obtained by different institutio ns, 200 laboratories from 26 countries have joined the UK national external quality assessment scheme for immunocytochemistry (NEQAS-ICC). Histologica l sections from breast cancers having low, medium, and high levels of oestr ogen receptor expression were sent to each of the laboratories for immunohi stochemical staining. The results obtained were evaluated for the sensitivi ty of detection, first by estimating threshold values of 1% and 10% of stai ned tumour cells, and second by the Quick score method, by a panel of four assessors judging individual sections independently on a single blind basis . The results were also evaluated using participants' own threshold values. Results-Over 80% of laboratories were able to demonstrate oestrogen recepto r positivity on the medium and high expressing tumours, but only 37% of lab oratories scored adequately on the low expressing tumour. Approximately one third of laboratories failed to register any positive staining in this tum our, while one third showed only minimal positivity. Conclusions-There is considerable interlaboratory variability, especially i n relation to the detection of breast cancers with low oestrogen receptor p ositivity, with a false negative rate of between 30% and 60%. This variabil ity appears to be caused by minor differences in methodology that may be re ctified by fine adjustment of overall technique.