Canadian Association of Pathologists-Association canadienne des pathologistes National Standards Committee for High Complexity Testing/Immunohistochemistry: guidelines for the preparation, release, and storage of unstained archived diagnostic tissue sections for immunohistochemistry.

OBJECTIVES: Formalin-fixed, paraffin-embedded unstained archived diagnostic tissue sections are frequently exchanged between clinical laboratories for immunohistochemical staining. The manner in which such sections are prepared represents a type of preanalytical variable that must be taken into account given the growing importance of immunohistochemical assays, especially predictive and prognostic tests, in personalized medicine. METHODS: Recommendations were derived from review of the literature and expert consensus of the Canadian Association of Pathologists-Association canadienne des pathologists National Standards Committee for High Complexity Testing/Immunohistochemistry. RESULTS: Relevant considerations include the type of glass slide on which to mount the unstained sections; the thickness of the tissue sections; the time from slide preparation to testing; the environment, particularly the temperature at which the unstained sections will be maintained prior to testing; the inclusion of on-slide positive control tissue where possible; and whether patient identifier(s) should be included on slide labels. CONCLUSIONS: Clear communication between requesting and releasing laboratories will facilitate the proper preparation of unstained sections and also ensure that applicable privacy considerations are addressed.

The laboratory score/reference method score ratio (LSRSR) is a novel tool for monitoring laboratory performance in immunohistochemistry proficiency testing of hormone receptors in breast cancer: the CIQC experience.

Canadian Immunohistochemistry Quality Control (CIQC) operates an academic proficiency testing (PT) program using a traditional expert panel-based qualitative assessment system. The image analysis approach is increasingly considered for use in PT to follow demand for precision in immunohistochemical test calibration. CIQC introduces and explores the usefulness of a novel image analysis-based tool, the laboratory score/reference method score ratio (LSRSR) for PT. Two CIQC runs with 33 and 57 participants, respectively, were analyzed for interlaboratory concordance for estrogen receptor results using expert panel-based and LSRSR systems. Samples included tissue microarrays with 40 tissue cores each. The LSRSR was calculated from participants' and reference laboratory H scores measured by image analysis. We found lower concordance with reference method results for participating laboratories by LSRSR than those reported by the expert panel; although the expert panel observed those differences, it was not able to measure them without LSRSR. LSRSR may be useful in monitoring laboratory performance for quantitative immunohistochemical testing.

Inappropriate calibration and optimisation of pan-keratin (pan-CK) and low molecular weight keratin (LMWCK) immunohistochemistry tests: Canadian Immunohistochemistry Quality Control (CIQC) experience.

AIMS: Pan-cytokeratin (pan-CK) and low molecular weight cytokeratin (LMWCK) tests are the most common immunohistochemistry (IHC) tests used to support evidence of epithelial differentiation. Canadian Immunohistochemistry Quality Control (CIQC), a new provider of proficiency testing for Canadian clinical IHC laboratories, has evaluated the performance of Canadian IHC laboratories in two proficiency testing challenges for both pan-CK and LMWCK. METHODS: CIQC has designed a 70-sample tissue microarray (TMA) for challenge 1 and a 30-sample TMA for challenge 2. There were 13 participants in challenge 1, and 62 in challenge 2. All results were evaluated and scored by CIQC assessors and compared with reference laboratory results. RESULTS: Participating laboratories often produced false-negative results that ranged from 20% to 80%. False-positive results were also detected. About half of participating clinical laboratories have inappropriately calibrated IHC tests for pan-CK and LMWCK, which are the most commonly used markers for demonstration of epithelial differentiation. The great majority of laboratories were not aware of the problem with calibration of pan-CK and LMWCK tests because of inappropriate selection of external positive controls and samples for optimisation of these tests. Benign liver and kidney are the most important tissues to include as positive controls for both pan-CK and LMWCK. CONCLUSIONS: Participation in external quality assurance is important for peer comparison and proper calibration of IHC tests, which is also helpful for appropriate selection of positive control material and material for optimisation of the tests.

Are endometrial polyps true cancer precursors?

OBJECTIVE: The purpose of this study was to assess whether endometrial polyps (EMPs) represent cancer precursors. STUDY DESIGN: Age standardized incidence ratios (SIRs) of histologically verified endometrial cancers (EmCas) were estimated in women with EMPs and in women with uterine leiomyomata, which is a condition that is unrelated to endometrial carcinogenesis. SIRs were calculated as the ratio of observed to expected EmCas based on age-specific incidence rates for female Montreal residents during the same period. RESULTS: Of 1467 women with EMPs, 125 (8.5%) had EmCa. Of 1138 patients with uterine leiomyomata, 133 (11.7%) had EmCa. The SIRs of EmCa for women with EMPs (odds ratio, 8.0; 95% confidence interval, 6.6-9.5) were significantly lower than that in women with leiomyomata (odds ratio, 19.1; 95% confidence interval, 16.0-22.6). Abnormal uterine bleeding was the main reason for evaluating patients with EMP with or without associated EmCa. CONCLUSION: The findings of higher EmCa incidence are consistent with enhanced detection opportunity rather than with the endometrial cancer precursor potential of EMPs.

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 kappa 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.