Penny Barnes

Canadian Association of Pathologists-Association canadienne des pathologistes National Standards Committee/Immunohistochemistry: best practice recommendations for standardization of immunohistochemistry tests.

Immunohistochemical and immunocytochemical assays are highly complex diagnostic analyses used to aid in the accurate identification and biologic characterization of tissue types in neoplastic and nonneoplastic diseases. Immunohistochemical tests are applied mainly to the diagnosis of neoplasms. Some immunohistochemical tests provide information of important prognostic and predictive value in selected human neoplasms and, as such, are often critical for the appropriate and effective treatment of patients. This document provides recommendations and opinions of the Canadian Association of Pathologists-Association canadienne des pathologistes National Standards Committee/Immunohistochemistry relevant to clinical immunohistochemical terminology, classification of immunohistochemical tests based on risk assessment, and quality control and quality assurance and summarizes matters to be considered for appropriate immunohistochemical/immunocytochemical test development, performance, and interpretation in diagnostic pathology and laboratory medicine.

Implementation of a Canadian external quality assurance program for breast cancer biomarkers: an initiative of Canadian Quality Control in immunohistochemistry (cIQc) and Canadian Association of Pathologists (CAP) National Standards Committee/Immunohistochemistry.

Immunohistochemistry results for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are used to guide breast carcinoma patient management and it is essential to monitor these tests in external quality assurance (EQA) programs. Canadian Immunohistochemistry Quality Control is a web-based program with novel approach to EQA. Canadian Immunohistochemistry Quality Control RUN2 included tissue microarray slides with 38 samples tested by 18 immunohistochemical laboratories. Deidentified results were posted for viewing at www.ciqc.ca including all used protocols matched with scanned slides for virtual microscopy and garrattograms. Sensitivity, specificity, Kendall W test (concordance between laboratories), and κ statistics (agreement with designated reference values) were calculated. Kappa values were within the target range (>0.8, or “near perfect” agreement) for 85% results. Kendall coefficient was 0.942 for estrogen receptor, 0.930 for progesterone receptor, and 0.958 for human epidermal growth factor receptor 2. The anonymous participation, quick feedback, and unrestricted full access in EQA results provides rapid insight into technical or interpretive deficiencies, allowing appropriate corrective action to be taken whereas the use of tissue microarrays enables meaningful statistical analysis.

Human Epidermal Growth Factor Receptor 2 Testing in Primary Breast Cancer in the Era of Standardized Testing: A Canadian Prospective Study

PURPOSE Therapies that target overexpression of human epidermal growth factor receptor 2 (HER2) rely on accurate and timely assessment of all patients with new diagnoses. This study examines HER2 testing of primary breast cancer tissue when performed with immunohistochemistry (IHC) and additional in situ hybridization (ISH) for negative cases (IHC 0/1+). The analysis focuses on the rate of false-negative HER2 tests, defined as IHC 0/1+ with an ISH ratio ≥ 2.0, in eight pathology centers across Canada. PATIENTS AND METHODS Whole sections of surgical resections or tissue microarrays (TMAs) from invasive breast carcinoma tissue were tested by both IHC and ISH using standardized local methods. Samples were scored by the local breast pathologist, and consecutive HER2-negative IHC results (IHC 0/1+) were compared with the corresponding fluorescence or silver ISH result. RESULTS Overall, 711 surgical excisions of primary breast cancer were analyzed by IHC and ISH; HER2 and chromosome 17 centromere (CEP17) counts were available in all cases. The overall rate of false-negative samples was 0.84% (six of 711 samples). Interpretable IHC and ISH scores were available in 1,212 cases from TMAs, and the overall rate of false-negative cases was 1.6% (16 of 978 cases). CONCLUSION Our observation confirms that IHC is an adequate test to predict negative HER2 status in primary breast cancer in surgical excision specimens, even when different antibodies and IHC platforms are used. The study supports the American Society of Clinical Oncology/College of American Pathologists and Canadian testing algorithms of using IHC followed by ISH for equivocal cases.

Canadian external quality assurance program for breast cancer biomarkers.

To the Editor: We wish to respond to the letter from Dr Flynn and Ms Schirripa regarding our recent report on our continuing nationwide efforts to improve immunohistochemical testing, including breast cancer biomarker testing, in Canada. They state unequivocally that there were misrepresentations in our paper, but do not indicate what they are. We would like to emphasize here that our paper does not evaluate or comment on the work of the Quality Management Program, Laboratory Services (their employer) at all, but rather on our own academic program. The methods and results of the Quality Management Program, Laboratory Services testing are not available to us and therefore could not be included in our discussion. As these alleged misrepresentations were not specifically identified, we are denied the opportunity to effectively respond. We cannot dismiss this failure to identify the alleged misrepresentations as an oversight, as it seems that Dr Flynn and Ms Schirrapa have chosen to use the forum provided by the ‘‘Letters to the Editor’’ to promote their program in vague general terms and create doubt about our program through allegations of ‘‘misrepresentations.’’ The Canadian Immunohistochemistry Quality Control provides the opportunity for Canadian laboratories to participate in their own national external quality assurance program for diagnostic immunohistochemistry and we are saddened that we are perceived as competition rather than collaborators of our Canadian colleagues, as we all have to face the difficult task of helping to raise standards of practice in this challenging area of clinical laboratory practice.