• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jclinpathJournal of Clinical PathologyCurrent TOCInstructions for authors
J Clin Pathol. Feb 2000; 53(2): 125–130.
PMCID: PMC1763294

Reliability of immunohistochemical demonstration of oestrogen receptors in routine practice: interlaboratory variance in the sensitivity of detection and evaluation of scoring systems


Aims—To investigate interlaboratory variance in the immunohistochemical (IHC) detection of oestrogen receptors so as to determine the rate of false negatives, which could adversely influence the decision to give adjuvant tamoxifen treatment.

Methods—To ensure that similar results are obtained by different institutions, 200 laboratories from 26 countries have joined the UK national external quality assessment scheme for immunocytochemistry (NEQAS-ICC). Histological sections from breast cancers having low, medium, and high levels of oestrogen receptor expression were sent to each of the laboratories for immunohistochemical staining. The results obtained were evaluated for the sensitivity of detection, first by estimating threshold values of 1% and 10% of stained 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 receptor positivity on the medium and high expressing tumours, but only 37% of laboratories scored adequately on the low expressing tumour. Approximately one third of laboratories failed to register any positive staining in this tumour, while one third showed only minimal positivity.

Conclusions—There is considerable interlaboratory variability, especially in relation to the detection of breast cancers with low oestrogen receptor positivity, with a false negative rate of between 30% and 60%. This variability appears to be caused by minor differences in methodology that may be rectified by fine adjustment of overall technique.

Key Words: immunohistochemistry • oestrogen receptors • interlaboratory variation

Full Text

The Full Text of this article is available as a PDF (158K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • al Saati T, Clamens S, Cohen-Knafo E, Faye JC, Prats H, Coindre JM, Wafflart J, Caverivière P, Bayard F, Delsol G. Production of monoclonal antibodies to human estrogen-receptor protein (ER) using recombinant ER (RER). Int J Cancer. 1993 Oct 21;55(4):651–654. [PubMed]
  • Hendricks JB, Wilkinson EJ. Comparison of two antibodies for evaluation of estrogen receptors in paraffin-embedded tumors. Mod Pathol. 1993 Nov;6(6):765–770. [PubMed]
  • Elledge RM, Osborne CK. Oestrogen receptors and breast cancer. BMJ. 1997 Jun 28;314(7098):1843–1844. [PMC free article] [PubMed]
  • Barnes DM, Millis RR, Beex LV, Thorpe SM, Leake RE. Increased use of immunohistochemistry for oestrogen receptor measurement in mammary carcinoma: the need for quality assurance. Eur J Cancer. 1998 Oct;34(11):1677–1682. [PubMed]
  • Reiner A, Neumeister B, Spona J, Reiner G, Schemper M, Jakesz R. Immunocytochemical localization of estrogen and progesterone receptor and prognosis in human primary breast cancer. Cancer Res. 1990 Nov 1;50(21):7057–7061. [PubMed]
  • Barnes DM, Harris WH, Smith P, Millis RR, Rubens RD. Immunohistochemical determination of oestrogen receptor: comparison of different methods of assessment of staining and correlation with clinical outcome of breast cancer patients. Br J Cancer. 1996 Nov;74(9):1445–1451. [PMC free article] [PubMed]
  • Pertschuk LP, Feldman JG, Kim YD, Braithwaite L, Schneider F, Braverman AS, Axiotis C. Estrogen receptor immunocytochemistry in paraffin embedded tissues with ER1D5 predicts breast cancer endocrine response more accurately than H222Sp gamma in frozen sections or cytosol-based ligand-binding assays. Cancer. 1996 Jun 15;77(12):2514–2519. [PubMed]
  • Fernö M, Andersson C, Fallenius G, Idvall I. Oestrogen receptor analysis of paraffin sections and cytosol samples of primary breast cancer in relation to outcome after adjuvant tamoxifen treatment. The South Sweden Breast Cancer Group. Acta Oncol. 1996;35(1):17–22. [PubMed]
  • Soubeyran I, Quénel N, Coindre JM, Bonichon F, Durand M, Wafflart J, Mauriac L. pS2 protein: a marker improving prediction of response to neoadjuvant tamoxifen in post-menopausal breast cancer patients. Br J Cancer. 1996 Oct;74(7):1120–1125. [PMC free article] [PubMed]
  • Kinsel LB, Szabo E, Greene GL, Konrath J, Leight GS, McCarty KS., Jr Immunocytochemical analysis of estrogen receptors as a predictor of prognosis in breast cancer patients: comparison with quantitative biochemical methods. Cancer Res. 1989 Feb 15;49(4):1052–1056. [PubMed]
  • Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998 Feb;11(2):155–168. [PubMed]
  • McCarty KS, Jr, Miller LS, Cox EB, Konrath J, McCarty KS., Sr Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med. 1985 Aug;109(8):716–721. [PubMed]

Figures and Tables

An external file that holds a picture, illustration, etc.
Object name is 99111.f1.jpg
Figure 1 Distribution of the results of the "Quick" score evaluation conducted on the three infiltrating ductal carcinomas (IDC), X, Y, Z, used at assessment. The bold line represents the median score, the bottom and top of the boxes, the 1st and 3rd ...
An external file that holds a picture, illustration, etc.
Object name is 99111.f2.jpg
Figure 2 The proportion of laboratories from which immunohistochemistry reliably demonstrated the intraductal carcinomas X, Y, Z as being oestrogen receptor positive. χ2 values were as follows:
An external file that holds a picture, illustration, etc.
Object name is 99111.f3.jpg
Figure 3 The proportions of 200 laboratories from which immunohistochemistry demonstrated either no nuclei, some nuclei but less than 10%, and 10% of more, in the "low" oestrogen receptor expressing infiltrating ductal carcinoma.

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Group


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...