Immunohistochemical detection using the new rabbit monoclonal antibody SP1 of estrogen receptor in breast cancer is superior to mouse monoclonal antibody 1D5 in predicting survival.
OBJECTIVE
Estrogen receptor (ER) expression predicts improved breast cancer-specific survival and reduced risk of recurrence and is targeted in breast cancer therapy. A high-quality antibody to identify ER-positive patients plays an important role in clinical decision making for women with breast cancer. This study evaluates immunohistochemistry using two anti-ER antibodies, a new rabbit monoclonal antibody (SP1) and the mouse monoclonal antibody (1D5), in relation to biochemical ER assay results and clinical data on survival and adjuvant systemic therapy.


METHODS
A population-based tissue microarray series of 4,150 invasive breast cancers was constructed. All patients had staging, pathology, treatment, and follow-up information. The median follow-up was 12.4 years and the median age at diagnosis 60 years. Survival analysis and log-rank tests were used to evaluate the prognostic value of ER status and correlations with clinical data.


RESULTS
Among the 4,105 samples interpretable for both antibodies, SP1 detected ER positivity in 69.5% and 1D5 in 63.1% of cases. Both monoclonal antibodies are demonstrated to be good prognostic indictors for breast cancer-specific and relapse-free survival. In multivariate analysis, including age, tumor size, grade, and lymphovascular and nodal status, SP1 was a better independent prognostic factor than 1D5. Among patients with discrepant ER results, the 8% of patients who were SP1 positive/1D5 negative showed good outcomes, and the 2% SP1-negative/1D5 positive had poor outcomes. Maintaining the same 92% specificity and 98% positive predictive value, SP1 is 8% more sensitive than 1D5 using biochemical assay as gold standard.


CONCLUSIONS
SP1 represents an improved standard for ER immunohistochemistry assessment in breast cancer.
Cheang
Maggie C U
MC
Genetic Pathology Evaluation Centre at Vancouver General Hospital, Prostate Centre, and University of British Columbia, Vancouver, British Columbia, Canada.
Treaba
Diana O
DO
Speers
Caroline H
CH
Olivotto
Ivo A
IA
Bajdik
Chris D
CD
Chia
Stephen K
SK
Goldstein
Lynn C
LC
Gelmon
Karen A
KA
Huntsman
David
D
Gilks
C Blake
CB
Nielsen
Torsten O
TO
Gown
Allen M
AM
D000818:Animals; D000911:Antibodies, Monoclonal; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007136:Immunoglobulins / Q000276:immunology; D007150:Immunohistochemistry / Q000379:methods*; D008207:Lymphatic Metastasis; D051379:Mice; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011817:Rabbits; D011960:Receptors, Estrogen / Q000032:analysis*; D012680:Sensitivity and Specificity; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D007136:Immunoglobulins; D011960:Receptors, Estrogen; C090698:SP1 antigen