Well-differentiated invasive breast cancers with equivocal HER2 immunohistochemistry: what is the yield of routine reflex in-situ hybridization testing?

AIMS: The 2013 American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) HER2 guidelines recommend testing all invasive breast cancers for HER2, typically with immunohistochemistry (IHC) followed by in-situ hybridization (ISH) when IHC is equivocal. As well-differentiated breast cancers are rarely HER2-positive, we assessed the value of routine reflex HER2 ISH testing for this subset of breast cancers. METHODS AND RESULTS: We collected HER2 IHC 2+ cases and fluorescence in-situ hybridization (FISH) data from primary breast cancers with well-differentiated tumour types (grade 1 ductal carcinomas, classic lobular carcinomas, tubular, cribriform and pure mucinous carcinomas) at our centre from 2010 to 2015. Haematoxylin and eosin (H&E) and IHC slides were reviewed to confirm tumour type, grade and IHC score based on ASCO/CAP 2013 guidelines and their recent revisions. Of 4633 invasive carcinomas, 1133 had a well-differentiated tumour type; 177 of these were HER2 IHC equivocal, three of which were low-level amplified by FISH (0.3% of all well-differentiated tumours). One amplified case was classic invasive lobular carcinoma and two were invasive ductal carcinomas, grade 1. One amplified case had chromosome 17 monosomy, and one was rescored as HER2 IHC 1+ upon review. 'Basolateral' staining was noted in one amplified case and in 65 of 174 (37.4%) non-amplified cases. This incomplete membranous staining pattern was observed in the majority of invasive ductal carcinomas that were rescored as 1+ according to the revised 2013 guidelines. CONCLUSIONS: The rate of HER2 amplification among well-differentiated breast cancers is very low. Basolateral staining in well-differentiated tumours may be overinterpreted as HER2 IHC 2+, but is rarely associated with HER2 amplification.

Impact of the 2013 American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing of invasive breast carcinoma: a focus on tumours assessed as 'equivocal' for HER2 gene amplification by fluorescence in-situ hybridization.

AIMS: The updated 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) human epidermal growth factor receptor 2 (HER2) testing guidelines include changes to HER2 in-situ hybridization (ISH) interpretation criteria. We conducted a retrospective review of a consecutive cohort of primary breast carcinomas to assess the impact of updated guidelines on HER2 classification and laboratory resource utilization, and to characterize the pathobiology of HER2 equivocal tumours. METHODS AND RESULTS: A total of 904 dual-probe HER2/chromosome enumeration probe (CEP17) FISH tests on invasive breast carcinomas were studied. Eighty-five (9.4%) cases had a classification change with the updated guidelines; 66 (7.3%) went from HER2-negative to -equivocal, 15 cases (1.7%) were reclassified as HER2-positive and four cases from HER2-equivocal to -negative. A subset of primary breast cancers, reported initially as HER2-negative but -equivocal by 2013 guidelines, was identified. Traditional pathological factors of this subset were compared to HER2-negative and -positive control cases. The three HER2 groups demonstrated statistically significant differences with respect to prognostic factors, including tumour size, grade and nodal involvement. CONCLUSIONS: The updated HER2 testing guidelines will result in the reclassification of approximately 9.4% of primary breast cancers with uncertainty regarding the clinical impact of this reclassification in the majority of cases. Resource utilization will increase as a result of the recommendation for retesting.

Physician Perspectives on Malnutrition Screening, Diagnosis, and Management: A Qualitative Analysis.

Malnutrition is an important clinical entity that is frequently underdiagnosed and undertreated, in part due to a lack of education and different perceptions by healthcare providers on its value in medical practice. Given this void, the purpose of this qualitative study was to explore physicians' clinical perspectives on malnutrition care, including its prevalence in their practice, and potential barriers that might preclude the delivery of malnutrition care. Using a directed content qualitative analysis approach, a total of 22 general and subspecialist physicians across three Canadian provinces were interviewed using a series of standardized questions developed by a multidisciplinary research team. Responses were transcribed and then analyzed using NVivo Version 14 software. While physicians recognized the importance of malnutrition screening and treatment, they did not view themselves as the primary drivers and often deferred this responsibility to dietitians. Lack of standard malnutrition screening, education amongst allied healthcare providers, time, personnel, and referral processes to have patients assessed and managed for malnutrition were also identified as contributing factors. For physicians, malnutrition education, standard malnutrition screening during patient encounters, and access to the necessary tools to manage malnutrition using a more centralized approach and standard referral process were viewed as strategies with the potential to improve the ability of the physician to identify and manage disease-related malnutrition and its negative consequences.

The Role of Hepatic Venous Pressure Gradient in the Management of Cirrhosis.

Quantifying the degree of portal hypertension provides useful information to estimate prognosis and to evaluate new therapies for portal hypertension. This quantification is done in clinical practice with the measurement of the hepatic venous pressure gradient. This article addresses the applications of measuring portal pressure in cirrhosis, including the differential diagnosis of portal hypertension; estimation of prognosis in cirrhosis, including preoperative evaluation before hepatic and extrahepatic surgery; assessment of the response to drug therapy (mainly in the context of drug development); and assessing the regression of portal hypertension syndrome.