Human epidermal growth factor receptor 2 (HER2) overexpression is present in approximately 15% of early invasive breast cancers, and is an important predictive and prognostic marker. The substantial benefits achieved with anti-HER2 targeted therapies in patients with HER2-positive breast cancer have emphasised the need for accurate assessment of HER2 status. Current data indicate that HER2 test accuracy improved following previous publication of guidelines and the implementation of an external quality assessment scheme with a decline in false-positive and false-negative rates. This paper provides an update of the guidelines for HER2 testing in the UK. The aim is to further improve the analytical validity and clinical utility of HER2 testing by providing guidelines of test performance parameters, and recommendations on the postanalytical interpretation of test results. HER2 status should be determined in all newly diagnosed and recurrent breast cancers. Testing involves immunohistochemistry with >10% complete strong membrane staining defining a positive status. In situ hybridisation, either fluorescent or bright field chromogenic, is used either upfront or in immunohistochemistry borderline cases to detect the presence of HER2 gene amplification. Situations where repeat HER2 testing is advised are outlined and the impact of genetic heterogeneity is discussed. Strict quality control and external quality assurance of validated assays are essential. Testing laboratories should perform ongoing competency assessment and proficiency tests and ensure the reliability and accuracy of the assay. Pathologists, oncologists and surgeons involved in test interpretation and clinical use should adhere to published guidelines and maintain accurate performance and consistent interpretation of test results.

Validation of immunohistochemistry (IHC) assays is a subject that is of great importance to clinical practice as well as basic research and clinical trials. When applied to clinical practice and focused on patient safety, validation of IHC assays creates objective evidence that IHC assays used for patient care are "fit-for-purpose." Validation of IHC assays needs to be properly informed by and modeled to assess the purpose of the IHC assay, which will further determine what sphere of validation is required, as well as the scope, type, and tier of technical validation. These concepts will be defined in this review, part 3 of the 4-part series "Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine."

Good quality of immunocytochemical staining can be achieved on cytology slides prepared and fixed in different ways as well as on cell blocks. Unified criteria for high-quality immunocytochemical staining and proper internal and external quality assurance could facilitate further improvement and standardization of immunocytochemistry on cytology samples.

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BackgroundAcute variceal bleeding (AVB) requires early therapeutic management by experienced endoscopists that often poses logistical challenges for hospitals. We assessed a different management concept with early application of haemostatic powder—which does not require high endoscopic expertise—added to conventional management in a randomised trial.MethodsCirrhotic patients with AVB received standard medical therapy and were randomised to either immediate endoscopy with haemostatic powder application within 2 hours of admission, followed by early elective endoscopy on the next day, that is, within 12–24 hours of admission for definitive treatment (study group) or to early elective endoscopy only (control group). In both groups, failures to achieve clinical haemostasis until the time of early elective endoscopy underwent rescue endoscopy with attempted conventional haemostasis. Primary outcome was endoscopic haemostasis at the elective endoscopy.ResultsOf 86 randomised patients with AVB, 5/43 in the study group required rescue endoscopy for failure of controlling spurting bleeding (n=4) after powder application or for early bleeding recurrence in one patient who died before repeating rescue endoscopy. In the control group, 13/43 patients required rescue endoscopic haemostasis for failure of clinical haemostasis (12%vs30%, p=0.034). In the remaining patients, early elective endoscopic haemostasis was achieved in all 38 patients in the study group, while all remaining 30 patients in the control group had fresh gastric blood or (10%) spurting bleeding at early elective endoscopy with successful haemostasis in all of them. Six-week survival was significantly improved in the study group (7%vs30%, p=0.006).ConclusionThe new concept of immediate powder application improves early clinical and endoscopic haemostasis. This simplified endoscopic approach may have an impact on early and 6-week survival.Trial registration numberNCT03061604.