Browsing by Author "McShane, Lisa M."

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    Analytical validation of a standardised scoring protocol for Ki67 immunohistochemistry on breast cancer excision whole sections: an international multicentre collaboration
    (Wiley, 2019-08) Leung, Samuel C. Y.; Nielsen, Torsten O.; Zabaglo, Lila A.; Arun, Indu; Badve, Sunil S.; Bane, Anita L.; Bartlett, John M. S.; Borgquist, Signe; Chang, Martin C.; Dodson, Andrew; Ehinger, Anna; Fineberg, Susan; Focke, Cornelia M.; Gao, Dongxia; Gown, Allen M.; Gutierrez, Carolina; Hugh, Judith C.; Kos, Zuzana; Lænkholm, Anne-Vibeke; Mastropasqua, Mauro G.; Moriya, Takuya; Nofech-Mozes, Sharon; Osborne, C. Kent; Penault-Llorca, Frédérique M.; Piper, Tammy; Sakatani, Takashi; Salgado, Roberto; Starczynski, Jane; Sugie, Tomoharu; van der Vegt, Bert; Viale, Giuseppe; Hayes, Daniel F.; McShane, Lisa M.; Dowsett, Mitch; Pathology and Laboratory Medicine, School of Medicine
    Aims The nuclear proliferation marker Ki67 assayed by immunohistochemistry has multiple potential uses in breast cancer, but an unacceptable level of interlaboratory variability has hampered its clinical utility. The International Ki67 in Breast Cancer Working Group has undertaken a systematic programme to determine whether Ki67 measurement can be analytically validated and standardised among laboratories. This study addresses whether acceptable scoring reproducibility can be achieved on excision whole sections. Methods and results Adjacent sections from 30 primary ER+ breast cancers were centrally stained for Ki67 and sections were circulated among 23 pathologists in 12 countries. All pathologists scored Ki67 by two methods: (i) global: four fields of 100 tumour cells each were selected to reflect observed heterogeneity in nuclear staining; (ii) hot‐spot: the field with highest apparent Ki67 index was selected and up to 500 cells scored. The intraclass correlation coefficient (ICC) for the global method [confidence interval (CI) = 0.87; 95% CI = 0.799–0.93] marginally met the prespecified success criterion (lower 95% CI ≥ 0.8), while the ICC for the hot‐spot method (0.83; 95% CI = 0.74–0.90) did not. Visually, interobserver concordance in location of selected hot‐spots varies between cases. The median times for scoring were 9 and 6 min for global and hot‐spot methods, respectively. Conclusions The global scoring method demonstrates adequate reproducibility to warrant next steps towards evaluation for technical and clinical validity in appropriate cohorts of cases. The time taken for scoring by either method is practical using counting software we are making publicly available. Establishment of external quality assessment schemes is likely to improve the reproducibility between laboratories further.
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    Analytical validation of a standardized scoring protocol for Ki67: phase 3 of an international multicenter collaboration
    (Nature, 2016) Leung, Samuel C. Y.; Nielsen, Torsten O.; Zabaglo, Lila; Arun, Indu; Badve, Sunil S.; Bane, Anita L.; Bartlett, John M. S.; Borgquist, Signe; Chang, Martin C.; Dodson, Andrew; Enos, Rebecca A.; Fineberg, Susan; Focke, Cornelia M.; Gao, Dongxia; Gown, Allen M.; Grabau, Dorthe; Gutierrez, Carolina; Hugh, Judith C.; Kos, Zuzana; Lænkholm, Anne-Vibeke; Lin, Ming-Gang; Mastropasqua, Mauro G.; Moriya, Takuya; Nofech-Mozes, Sharon; Osborne, C. Kent; Penault-Llorca, Frédérique M.; Piper, Tammy; Sakatani, Takashi; Salgado, Roberto; Starczynski, Jane; Viale, Giuseppe; Hayes, Daniel F.; McShane, Lisa M.; Dowsett, Mitch; Pathology and Laboratory Medicine, School of Medicine
    Pathological analysis of the nuclear proliferation biomarker Ki67 has multiple potential roles in breast and other cancers. However, clinical utility of the immunohistochemical (IHC) assay for Ki67 immunohistochemistry has been hampered by unacceptable between-laboratory analytical variability. The International Ki67 Working Group has conducted a series of studies aiming to decrease this variability and improve the evaluation of Ki67. This study tries to assess whether acceptable performance can be achieved on prestained core-cut biopsies using a standardized scoring method. Sections from 30 primary ER+ breast cancer core biopsies were centrally stained for Ki67 and circulated among 22 laboratories in 11 countries. Each laboratory scored Ki67 using three methods: (1) global (4 fields of 100 cells each); (2) weighted global (same as global but weighted by estimated percentages of total area); and (3) hot-spot (single field of 500 cells). The intraclass correlation coefficient (ICC), a measure of interlaboratory agreement, for the unweighted global method (0.87; 95% credible interval (CI): 0.81–0.93) met the prespecified success criterion for scoring reproducibility, whereas that for the weighted global (0.87; 95% CI: 0.7999–0.93) and hot-spot methods (0.84; 95% CI: 0.77–0.92) marginally failed to do so. The unweighted global assessment of Ki67 IHC analysis on core biopsies met the prespecified criterion of success for scoring reproducibility. A few cases still showed large scoring discrepancies. Establishment of external quality assessment schemes is likely to improve the agreement between laboratories further. Additional evaluations are needed to assess staining variability and clinical validity in appropriate cohorts of samples.
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    Assessment of Ki67 in Breast Cancer: Updated Recommendations From the International Ki67 in Breast Cancer Working Group
    (Oxford University Press, 2021) Nielsen, Torsten O.; Leung, Samuel C. Y.; Rimm, David L.; Dodson, Andrew; Acs, Balazs; Badve, Sunil; Denkert, Carsten; Ellis, Matthew J.; Fineberg, Susan; Flowers, Margaret; Kreipe, Hans H.; Laenkholm, Anne-Vibeke; Pan, Hongchao; Penault-Llorca, Frédérique M.; Polley, Mei-Yin; Salgado, Roberto; Smith, Ian E.; Sugie, Tomoharu; Bartlett, John M. S.; McShane, Lisa M.; Dowsett, Mitch; Hayes, Daniel F.; Pathology and Laboratory Medicine, School of Medicine
    Ki67 immunohistochemistry (IHC), commonly used as a proliferation marker in breast cancer, has limited value for treatment decisions due to questionable analytical validity. The International Ki67 in Breast Cancer Working Group (IKWG) consensus meeting, held in October 2019, assessed the current evidence for Ki67 IHC analytical validity and clinical utility in breast cancer, including the series of scoring studies the IKWG conducted on centrally stained tissues. Consensus observations and recommendations are: 1) as for estrogen receptor and HER2 testing, preanalytical handling considerations are critical; 2) a standardized visual scoring method has been established and is recommended for adoption; 3) participation in and evaluation of quality assurance and quality control programs is recommended to maintain analytical validity; and 4) the IKWG accepted that Ki67 IHC as a prognostic marker in breast cancer has clinical validity but concluded that clinical utility is evident only for prognosis estimation in anatomically favorable estrogen receptor-positive and HER2-negative patients to identify those who do not need adjuvant chemotherapy. In this T1-2, N0-1 patient group, the IKWG consensus is that Ki67 5% or less, or 30% or more, can be used to estimate prognosis. In conclusion, analytical validity of Ki67 IHC can be reached with careful attention to preanalytical issues and calibrated standardized visual scoring. Currently, clinical utility of Ki67 IHC in breast cancer care remains limited to prognosis assessment in stage I or II breast cancer. Further development of automated scoring might help to overcome some current limitations.
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    Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update
    (ASCO, 2018) Wolff, Antonio C.; Hammond, M. Elizabeth Hale; Allison, Kimberly H.; Harvey, Brittany E.; Mangu, Pamela B.; Bartlett, John M. S.; Bilous, Michael; Ellis, Ian O.; Fitzgibbons, Patrick; Hanna, Wedad; Jenkins, Robert B.; Press, Michael F.; Spears, Patricia A.; Vance, Gail H.; Viale, Giuseppe; McShane, Lisa M.; Dowsett, Mitchell; Medical and Molecular Genetics, School of Medicine
    Purpose To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline. Methods Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations. Recommendations Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in > 10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not “must”) be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended work-up for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 (HER2/chromosome enumeration probe 17 [CEP17] ratio ≥ 2.0; average HER2 copy number < 4.0 signals per cell), ISH group 3 (HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 6.0 signals per cell), and ISH group 4 (HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 4.0 and < 6.0 signals per cell). The diagnostic approach includes more rigorous interpretation criteria for ISH and requires concomitant IHC review for dual-probe ISH groups 2 to 4 to arrive at the most accurate HER2 status designation (positive or negative) based on combined interpretation of the ISH and IHC assays. The Expert Panel recommends that laboratories using single-probe ISH assays include concomitant IHC review as part of the interpretation of all single-probe ISH assay results.