Recommendations for validating estrogen and progesterone receptor immunohistochemistry assays

Department of Pathology, St Jude Medical Center, Fullerton, California 92835, USA.
Archives of pathology & laboratory medicine (Impact Factor: 2.84). 06/2010; 134(6):930-5. DOI: 10.1043/1543-2165-134.6.930
Source: PubMed


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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    • "method of antigen retrieval, antibody, antibody detection and staining method), as well as interpretative methods (e.g. scoring method and thresholds/ cut-offs) [11] [12]. as ihC techniques are evolving, continuous validation is required to ensure consistent reporting [5] [12]. The importance of quality assurance is highlighted in guidelines and recommendations , and several organisations perform external proficiency testing, e.g. the united kingdom national External Quality assessment Scheme for immunocytochemistry (uk nEQaS), the College of american Pathologists (CaP), and the organisation nordic immunohistochemical Quality Control (nordiQC), as well as other smaller national organisations [6,8,11–16]. "
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    ABSTRACT: Biomarkers are crucial for decisions regarding adjuvant therapy in primary breast cancer, and their correct assessment is therefore of the utmost importance. To investigate the concordance between Swedish pathology departments and a reference laboratory, for routine analysis of oestrogen receptor (ER), progesterone receptor (PR), Ki67, and human epidermal growth factor receptor 2 (HER2), alone, and in combination (St Gallen subtypes). This survey included 27 of the 28 pathology laboratories in Sweden, covering 98% of cases of primary breast cancer surgery in Sweden. Paraffin-embedded tumour blocks (n = 270) were collected and sent to the central reference laboratory, together with the originally stained slides, for re-analysis. The primary evaluations were previously performed according to national Swedish guidelines, without any knowledge of the subsequent central assessment. The agreement for ER, PR, and Ki67 was 99% [kappa value (κ) = 0.95], 95% (κ = 0.85), and 85% (κ = 0.70), respectively. The agreement for HER2 (0/1 + vs. 2+/3+) was 85% (κ = 0.64), but when equivocal tumours were further analysed with in situ hybridisation, only one discrepancy was observed. Discrepancies between results for ER and PR seem to be explained by analytical differences, whereas the interpretation of staining seems to be more critical for Ki67 and HER2 immunohistochemistry. The agreement between the results from the Swedish laboratories and the reference laboratory, based on the St Gallen subtypes, was 88% (κ = 0.81). When applying national guidelines, highly reproducible results were obtained in routine assessment of breast cancer biomarkers, and the results of this study confirm the clinical utility of these markers for decisions regarding the treatment of primary breast cancer.
    No preview · Article · May 2015 · Acta oncologica (Stockholm, Sweden)
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    • "Tumours were considered to be positive for ER and PR when nuclear positivity was observed in >1% of neoplastic cells [32]. HER2 scoring was performed according to the UK accepted diagnosis criteria [33]. "
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    ABSTRACT: Basal-like breast carcinoma (BLBC) has attracted considerable attention over the past few years. It has been suggested that tumours expressing basal markers have a more aggressive clinical behaviour. However, a molecular basis for this disease remains unclear, and it lacks currently used therapeutic targets. Therefore developing a novel treatment strategy is crucial for improving the prognosis. The aim of this study was to characterise the immunohistochemical (IHC) expression of p16 in patients with BLBC compared with non-BLBC. Eighty-five cases of grade-3 invasive ductal carcinomas not otherwise specified (IDC-NOS) were analyzed. Immunohistochemical stains for oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor type 2 (HER2), cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR) and p16 were performed. BLBC was defined as ER-, PR-, Her2- and CK5/6+, and/or EGFR+. Twenty cases were categorised as BLBC versus 65 as non-basal. High mitotic count and presence of necrosis were associated with basal-like phenotype. Distant metastasis developed in 40% of cases of BLBC with frequent spread to brain and lung. p16 had significantly higher expression in the basal subgroup (80% versus 50.8%, P = 0.04). Patients with BLBCs were found to have a lower disease-free survival (DFS) rate (60% versus 70.8%, P = 0.03). BLBC typically demonstrates a unique profile. p16 is frequently expressed in breast cancers with basal-like phenotype; this suggests that p16 may play a role in the poor prognosis of this tumour, and it may be used in the development of a targeted therapy that will result in improved patient prognostication and outcome.
    Full-text · Article · May 2013 · ecancermedicalscience
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    • "In 2005 a breast nurse was introduced to facilitate the patient’s journey through the multidisciplinary track and to be a gate-keeper of the clinical pathway. From January 2006 onwards immunohistochemical assessment of estrogen receptor, progesterone receptor and c-erbB-2 was standardized using FDA approved FARM DX and Herceptest Dako immunohistochemistry (Dako, Carpinteria, CA, USA) [16,17]. In January 2007 the Breast Clinic of the Sint-Augustinus Hospital was formally opened. "
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    ABSTRACT: Background Due to increasing the complexity of breast cancer treatment it is of paramount importance to develop structured care in order to avoid a chaotic and non-consistent management of patients. Clinical pathways, a result of the adaptation of the documents used in industrial quality management namely the Standard Operating Procedures, can be used to improve efficiency and quality of care. They also aim to re-centre the focus on the patient’s overall journey, rather than the contribution of each specialty or caring function independently. Methods The effect of the implementation and prospective systematic evaluation of a clinical care pathway for the management of patients with early breast cancer in a single breast unit is evaluated over a long time interval (between 2002 and 2010). Annual analysis of predefined clinical outcome measures, service indicators, team indicators, process indicators and financial indicators was performed. Pathway quality control meetings were organized at least once a year. Systematic feedback was given to the team members, and if necessary the pathway was adapted according to evidence based literature data and in house pathway related data in order to improve quality. Results The annual number of patients included in the pathway (289 vs. 390, P <0.01), proportion of patients with Tis-T1 tumors (42% vs. 58%, P <0.01), negative lymph nodes (44% vs. 58%, P <0.01) and no metastases at diagnosis (91.5% vs. 95.9%) has risen significantly between 2002 and 2010. Evolution of mandatory quality indicators defined by EUSOMA shows a significant improvement of quality of cancer care. Particularly, the proportion of patients having anti-hormonal therapy (84.8% vs. 97.4%, P = 0.002) and adjuvant chemotherapy according to the guidelines (72% vs. 95.6%, P = 0.028) increased dramatically. Patient satisfaction improved significantly (P <0.05). Progression free 4-year survival was significantly higher for all patients, for T1 tumors only and for T2-T4 tumors only, treated between 2006 to 2008 compared to between 1999 to 2002 and 2003 to 2005 (P = 0.006, P = 0.05, P = 0.06, respectively). Overall 4-year survival of the entire population treated between 2006 and 2008 was significantly better (P = 0.05). Conclusions Although the patient characteristics changed over the years due to better screening, this clinical pathway and regular audit of quality indicators for the treatment of patients with operable breast cancer proved to be important tools to improve the quality of care, patient satisfaction and outcome.
    Full-text · Article · Mar 2013 · World Journal of Surgical Oncology
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