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Abstract
Purpose
The expression of hormone receptors is the most reliable factor for predicting the responsiveness to hormonal therapy. At present, immunohistochemistry (IHC) is considered as a practically reliable method. This study was designed to examine the interlaboratory variance in immunohistochemical assays for estrogen receptor (ER) and progesterone receptor (PR) in Korea.
Methods
The Korean Study Group for Breast Pathology (KSGBP) made a questionnaire to know the current situation in HR assay in Korea. The questionnaire was sent to the members of KSGBP by e-mail, which were included eight questions relating to tissue handling, ER/PR IHC procedure and interpretation method. Forty laboratories replied with the completed questionnaire.
Results
All 40 laboratories were using formalin as a fixative. Pretreatment was performed using six different methods including autoclave (25%), microwave (30%) and full autostainer (15%). Primary antibodies for ER were SP1 in 40%, 6F11 in 27.5% and 1D5 in 32.5%. Primary antibodies for PR were more variable (seven clones) than those for ER. Interpretation method used was Allred system in 20%, modified Allred system in 15%, report the % of positive tumor cells in 45%, positive/ negative in 15% and others in 5%. The expression rate of ER was ranged from 45.6% to 93% (mean 63.5%) and the expression rate of PR was ranged from 27% to 90% (mean 59.1%). The differences according to the numbers of breast cancer in each institute, primary antibodies, detection systems and interpretation methods did not influence to the expression rate of ER/PR, statistically (p>0.05).
Conclusion
In Korea, the interlaboratory variance in ER/PR IHC procedure was too huge to make a standardized method. We suggest the proper quality control program such as ER/PR staining with positive internal and external controls and negative control might be better to aim at getting similar results among the different laboratories rather than trying to standardize the procedure.
Figures and Tables
Figure 1
The differences according to the numbers of breast cancer cases at each institute (A), the antigen retrieval methods (B), the ER primary antibodies (C), the detection systems (D) and the interpretation methods (E) did not statistically influence the expression rate of ER and the differences according to the PR primary antibodies (F) did not statistically influence the expression rate of PR.
ER=estrogen receptor; PC=pressure cooker; polymer=polymer detection system; ABC/LSAB=avidin-biotin-enzyme complex/labeled streptavidin-biotin; %=% of positively stained tumor cells; Allred=Allred or modified Allred system; Dichotomy=posive vs negative.
Table 2
Applied antigen retrieval system, temperature and time for ER/PR IHC*
ER=estrogen receptor; PR=progesterone receptor; IHC=immunohistochemistry; AR=antigen retrieval; Temp=temperature; n=number of hospital; PC=pressure cooker; A=autoimmunostainer.
*One hospital applied different methods for ER and PR and method for ER was described here; †Includes Ventana autostainer and Leica autostainer; ‡LabVision autostainer with PT module.
Table 6
Interpretation methods for ER/PR IHC
ER=estrogen receptor; PR=progesterone receptor; IHC=immunohistochemistry.
*Negative, positive (11-25%), positive (26-50%), positive (51-75%), positive (76-100%); 1 (<10%), 2 (11-1/3%), 3 (1/3-2/3%), 4 (>2/3%); 0, 1+ (<10%), 2+ (11-50%), 3+ (>50%); †Included if information about fraction and intensity of stained tumor cells contained; ‡Using TMA, negative, 1+ (>10% and mild intensity), 2+ (>10% and moderate intensity), 3+ (>10% and severe intensity); negative (>5%), 1+ (5-20% and weak intensity), 2+ (20-50% and inermediate intensity), 3+ (>50% and strong intensity).
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