Semi-quantitative Immunohistochemical Assay versus oncotype DX® qRT-PCR Assay for Estrogen and Progesterone Receptors

An Independent Quality Assurance Study

James A Kraus; David J Dabbs; Sushil Beriwal; Rohit Bhargava


Mod Pathol. 2012;25(6):869-876. 

In This Article

Abstract and Introduction


Estrogen receptor (ER) status is a strong predictor of response to hormonal therapy in breast cancer patients. Presence of ER and level of expression have been shown to correlate with time to recurrence in patients undergoing therapy with tamoxifen or aromatase inhibitors. Risk reduction is also known to occur in ER-negative, progesterone receptor (PR)-positive patients treated with hormonal therapy. Since the 1990s, immunohistochemistry has been the primary method for assessing hormone receptor status. Recently, as a component of its oncotype DX® assay, Genomic Health began reporting quantitative estrogen and PR results determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). As part of an ongoing quality assurance program at our institution, we reviewed 464 breast cancer cases evaluated by both immunohistochemistry and oncotype DX® assay for estrogen and PR. We found good correlation for ER status between both assays (98.9% concordance), with immunohistochemistry being slightly more sensitive. Concordance for PR was 94.2% between immunohistochemistry and qRT-PCR with immunohistochemistry again more sensitive than RT-PCR. The results also showed linear correlation between immunohistochemistry H-scores and qRT-PCR expression values for ER (correlation coefficient of 0.579), and PR (correlation coefficient of 0.685). Due to the higher sensitivity of hormone receptor immunohistochemistry and additional advantages (ie preservation of morphology, less expensive, faster, more convenient), we conclude immunohistochemistry is preferable to qRT-PCR for determination of estrogen and PR expression.


Estrogen receptor (ER) status is a proven prognostic marker in breast cancer; however, its main clinical value is its ability to predict response to hormonal therapy. Most laboratories in the United States use immunohistochemistry to determine ER and progesterone receptor (PR) results on primary breast carcinomas. However, the method of reporting hormone receptor immunohistochemical results has been quite controversial over the years. The recent American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline recommendations for hormonal immunohistochemistry testing have suggested that although the likelihood of response to hormonal therapy appears to be directly related to the amount of hormone receptor expressed in tumor cells, patients with as little as 1% hormone receptor expression may still benefit from hormonal therapy.[1] This suggests potential benefit for reporting even very low levels of hormone receptor positivity, and the ASCO/CAP guidelines further recommend reporting both the proportion and intensity of hormone receptor protein expression in a semiquantitative manner.[1]

Oncotype DX® (Genomic Health, Redwood City, CA, USA) is a commercial assay designed to assess tumor recurrence probability in node-negative ER-positive breast cancers. It utilizes quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to analyze the expression of 21 genes (16 cancer-related and 5 control genes) to provide an estimated distant disease recurrence score ranging from 0 to 100.[2] The recurrence score was determined on the basis of national surgical adjuvant breast and bowel project training set data and proprietary analytic methods. Currently the test is widely used by oncologists for the optimization of clinical management. Recently, Genomic Health began reporting separate ER and PR expression units (compared with reference genes) to provide a qRT-PCR measurement of hormone receptor status.

As part of an ongoing quality assurance program at our institution, we previously reported pilot data comparing hormone receptor expression between immunohistochemistry and qRT-PCR.[3] The objective of the current study was to expand on this comparison utilizing a much larger dataset.


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