The prevalence of immunohistochemically determined oestrogen receptor positivity in primary breast cancer is dependent on the choice of antibody and method of heat-induced epitope retrieval - prognostic implications?
BACKGROUND
Oestrogen receptor (ER) status is important for the choice of systemic treatment of breast cancer patients. However, most data from randomised trials on the effect of adjuvant endocrine therapy according to ER status are based on the cytosol methods. Comparisons with immunohistochemical methods have given similar results. The aim of the present study was to examine whether different ER antibodies and heat-induced epitope retrieval (HIER) methods influence the prevalence of ER-positivity in primary breast cancer.


METHODS
This study is based on patients included in a clinical trial designed to compare the effect of two years of adjuvant tamoxifen versus no adjuvant systemic treatment in premenopausal women. From 1986 to 1991, 564 patients from two study centres in Sweden were enrolled and randomised. Patients were randomised independently of ER status. In the present study, ER status was assessed on tissue microarrays with the three different ER antibody/HIER combinations: 1D5 in citrate pH 6 (n = 390), SP1 in Tris pH 9 (n = 390) and PharmDx in citrate pH 6 (n = 361).


RESULTS
At cut-offs of 1% and 10%, respectively, the prevalence of ER-positivity was higher with SP1 (75% and 72%) compared with 1D5 (68% and 66%) and PharmDx (66% and 62%). At these cut-offs, patients in the discordant groups (SP1-positive and 1D5-negative) seem to have a prognosis intermediate between those of the double-positive and double-negative groups. Comparison with the ER status determined by the cytosol-based methods in the discordant group also showed an intermediate pattern. The repeatability was good for all antibodies and cut-offs, with overall agreement ≥ 93%.


CONCLUSIONS
The present study shows that the choice of antibody and HIER method influences the prevalence of ER-positivity. We suggest that this be taken into consideration when choosing a cut-off for clinical decision making.
Department of Pathology, Skåne University Hospital , Lund , Sweden.
Dorthe Aamand
DA
Grabau
Pär-Ola
PO
Bendahl
Lisa
L
Rydén
Olle
O
Stål
Mårten
M
Fernö
D000328:Adult; D000911:Antibodies, Monoclonal; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000939:Epitopes / Q000302:isolation & purification*; D005260:Female; D005500:Follow-Up Studies; D006358:Hot Temperature; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods*; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism*; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use; D046888:Tissue Array Analysis
D000911:Antibodies, Monoclonal; D018931:Antineoplastic Agents, Hormonal; D000939:Epitopes; D011960:Receptors, Estrogen; D013629:Tamoxifen