Digital image analysis of Ki67 in hot spots is superior to both manual Ki67 and mitotic counts in breast cancer

Autor:	Lena Wedlund, Johan Hartman, Stephanie Robertson, Michael Friis Lippert, Mattias Rantalainen, Gustav Stålhammar, Jonas Bergh
Rok vydání:	2018
Předmět:	Adult 0301 basic medicine Oncology medicine.medical_specialty Histology Breast Neoplasms Kaplan-Meier Estimate Sensitivity and Specificity Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Breast cancer Internal medicine Image Interpretation Computer-Assisted Biomarkers Tumor medicine Humans Clinical significance Mitosis Lymph node Pathological Aged business.industry Hazard ratio General Medicine Middle Aged Prognosis medicine.disease Ki-67 Antigen 030104 developmental biology medicine.anatomical_structure ROC Curve Area Under Curve 030220 oncology & carcinogenesis Digital image analysis Immunohistochemistry Female business
Zdroj:	Histopathology. 72:974-989
ISSN:	0309-0167
DOI:	10.1111/his.13452
Popis:	Aims During pathological examination of breast tumours, proliferative activity is routinely evaluated by a count of mitoses. Adding immunohistochemical stains of Ki67 provides extra prognostic and predictive information. However, the currently used methods for these evaluations suffer from imperfect reproducibility. It is still unclear whether analysis of Ki67 should be performed in hot spots, in the tumour periphery, or as an average of the whole tumour section. The aim of this study was to compare the clinical relevance of mitoses, Ki67 and phosphohistone H3 in two cohorts of primary breast cancer specimens (total n = 294). Methods and results Both manual and digital image analysis scores were evaluated for sensitivity and specificity for luminal B versus A subtype as defined by PAM50 gene expression assays, for high versus low transcriptomic grade, for axillary lymph node status, and for prognostic value in terms of prediction of overall and relapse-free survival. Digital image analysis of Ki67 outperformed the other markers, especially in hot spots. Tumours with high Ki67 expression and high numbers of phosphohistone H3-positive cells had significantly increased hazard ratios for all-cause mortality within 10 years from diagnosis. Replacing manual mitotic counts with digital image analysis of Ki67 in hot spots increased the differences in overall survival between the highest and lowest histological grades, and added significant prognostic information. Conclusions Digital image analysis of Ki67 in hot spots is the marker of choice for routine analysis of proliferation in breast cancer.
Databáze:	OpenAIRE
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