Recommendations for validating estrogen and progesterone receptor immunohistochemistry assays
ABSTRACT Estrogen receptor and progesterone receptor status is assessed on all newly diagnosed, invasive breast carcinomas and in recurrences to determine patient eligibility for hormonal therapy, but 10% to 20% of estrogen receptor and progesterone receptor test results are discordant when tested in multiple laboratories.
To define the analytic (technical) validation requirements for estrogen receptor and progesterone receptor immunohistochemistry assays used to select patients for hormonal therapy.
Literature review and expert consensus.
A standardized process for initial test validation is described. We believe adoption of this process will improve the accuracy of hormone-receptor testing, reduce interlaboratory variation, and minimize false-positive and false-negative results. Required ongoing assay assessment procedures are also described.
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- "Based on the histologic subtype, tumors were assigned to one of the following groups: 1) invasive ductal carcinoma not otherwise specified or any other special type of invasive ductal carcinoma, 2) invasive lobular carcinoma, 3) mixed ductal and lobular carcinoma, or 4) adenocarcinoma with spindle cell metaplasia and metaplastic carcinoma. Tumors were considered to be positive for ER or PR when nuclear reactivity was observed in at least 1% of neoplastic cells with an intensity of 3+ . The expression of Her2 was classified according to the Hercept Test assay's scoring system, which includes four categories , namely, 0, 1+, 2+, and 3+, based on the intensity and proportion of membrane staining in tumor cells. "
ABSTRACT: Glucose transporter 1 (Glut-1) is a facilitative glucose transporter expressed in many cancers including breast cancer. Basal-like breast cancer (BLBC) is a high-risk disease associated with poor prognosis and lacks the benefit of targeted therapy. The aim of this study was to characterize the immunohistochemical (IHC) expression of Glut-1 in patients with BLBC compared with non-BLBC. We identified 523 cases of invasive breast carcinoma from our database. The clinicopathologic findings and the biologic markers including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2) status were reviewed. IHC stains for cytokeratin 5/6 (CK5/6), epidermal growth factor receptor (EGFR), p53, and Glut-1 were performed on tissue microarray using standard procedures. BLBC was defined as ER-,PR-, Her2-, and CK5/6+ and/or EGFR+. Of informative cases, 14.7% were categorized as BLBC versus 85.3% as non-BLBC. Glut-1 was expressed in 42 (76.4%) of 55 BLBCs, whereas only 55 (23.8%) of 231 non-BLBCs showed immunostaining for Glut-1 (P < .001). Overall, Glut-1 expression was significantly associated with high histologic grade, ER negativity, PR negativity, CK5/6 positivity, EGFR expression, and high p53 expression (P < .001). However, there was no correlation between Glut-1 immunostaining and patient's outcome. Our results show that Glut-1 is significantly associated with BLBC and might be a potential therapeutic target for this aggressive subgroup of breast cancer, and this warrants further investigations.Translational oncology 12/2011; 4(6):321-7. DOI:10.1593/tlo.11256 · 3.40 Impact Factor
Chapter: Quality Management and Regulation[Show abstract] [Hide abstract]
ABSTRACT: Immunohistochemistry testing is highly complex with multiple steps. Assuring the optimum performance of your immunohistochemistry laboratory requires attention to numerous quality monitors. For testing performed on patient specimens, there are also additional regulatory requirements. This chapter answers questions about best practices in quality management in preanalytic, analytic, and postanalytic phases of the total immunohistochemistry test providing examples of possible quality improvement opportunities. It also provides information related to CLIA and FDA regulatory oversight medical devices, in vitro diagnostics (IVD), and analyte-specific reagents (ASR). With regard to immunohistochemistry laboratory accreditation, the final portion of this chapter draws attention to current best practice guidelines of the College of American Pathologists (CAP) relating to immunohistochemistry to prepare for inspection. KeywordsQuality-Regulation-CLIA-FDA-ASR-IVD-Controls-Validation-Inspection01/1970: pages 1-15;
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ABSTRACT: To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers. The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance. Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in preanalytic variables, thresholds for positivity, and interpretation criteria. The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.Archives of pathology & laboratory medicine 06/2010; 134(6):907-22. DOI:10.1043/1543-2165-134.6.907 · 2.88 Impact Factor