High‐throughput automated scoring of Ki67 in breast cancer tissue microarrays from the Breast Cancer Association Consortium
نویسندگان
چکیده
Automated methods are needed to facilitate high-throughput and reproducible scoring of Ki67 and other markers in breast cancer tissue microarrays (TMAs) in large-scale studies. To address this need, we developed an automated protocol for Ki67 scoring and evaluated its performance in studies from the Breast Cancer Association Consortium. We utilized 166 TMAs containing 16,953 tumour cores representing 9,059 breast cancer cases, from 13 studies, with information on other clinical and pathological characteristics. TMAs were stained for Ki67 using standard immunohistochemical procedures, and scanned and digitized using the Ariol system. An automated algorithm was developed for the scoring of Ki67, and scores were compared to computer assisted visual (CAV) scores in a subset of 15 TMAs in a training set. We also assessed the correlation between automated Ki67 scores and other clinical and pathological characteristics. Overall, we observed good discriminatory accuracy (AUC = 85%) and good agreement (kappa = 0.64) between the automated and CAV scoring methods in the training set. The performance of the automated method varied by TMA (kappa range= 0.37-0.87) and study (kappa range = 0.39-0.69). The automated method performed better in satisfactory cores (kappa = 0.68) than suboptimal (kappa = 0.51) cores (p-value for comparison = 0.005); and among cores with higher total nuclei counted by the machine (4,000-4,500 cells: kappa = 0.78) than those with lower counts (50-500 cells: kappa = 0.41; p-value = 0.010). Among the 9,059 cases in this study, the correlations between automated Ki67 and clinical and pathological characteristics were found to be in the expected directions. Our findings indicate that automated scoring of Ki67 can be an efficient method to obtain good quality data across large numbers of TMAs from multicentre studies. However, robust algorithm development and rigorous pre- and post-analytical quality control procedures are necessary in order to ensure satisfactory performance.
منابع مشابه
Possible Association of CD68 Positive Macrophages with Some other Prognostic Factors (ki67, ER, PR, Her2 neu) in Primary Breast Cancer and Axillary Lymph Node Metastasis
Background: Breast cancer is formed of a neoplastic component (epithelial) and a non-neoplastic component (stroma). Stromal- stromal and tumor- stromal interactions have been shown in the regulation of cancer cell growth, metastatic capacity and outcome of treatment. Tumor-associated macrophages (TAMs) are a component of tumor stroma reactionsand are considered as an important ...
متن کاملBovine Leukemia Virus Presence in Breast Tissue of Argentinian Females and Its Association With Cell Proliferation and Prognosis Markers
Abstract Introduction: Bovine leukemia virus (BLV) causes enzootic bovine leukemia, andis closely related to human T-lymphotropic virus type 1. It expresses microRNAs of unknown function and codes Tax, the protein that mediates malignant transformation. BLV is capable of infecting B- and T-lymphocytes, endothelial cells, and mammary epithelial cells of cattle. Several studies demonstrated the ...
متن کاملBovine Leukemia Virus Presence in Breast Tissue of Argentinian Females and Its Association With Cell Proliferation and Prognosis Markers
Abstract Introduction: Bovine leukemia virus (BLV) causes enzootic bovine leukemia, andis closely related to human T-lymphotropic virus type 1. It expresses microRNAs of unknown function and codes Tax, the protein that mediates malignant transformation. BLV is capable of infecting B- and T-lymphocytes, endothelial cells, and mammary epithelial cells of cattle. Several studies demonstrated the ...
متن کاملPrognostic Significance of Reduction in Ki67 Index After Neoadjuvant Chemotherapy in Patients With Breast Cancer in Kerman Between 2009 And 2014
Background and objective:Breast cancer is the most common malignancy among women. The Neoadjuvant chemotherapy is the treatment of choice for non-operable tumors. The Ki67 is a proliferation marker that can be used to predict the therapeutic response to chemotherapy and the patients' prognosis. Methods: This retrospective study was carri...
متن کاملStandardized Ki67 Diagnostics Using Automated Scoring--Clinical Validation in the GeparTrio Breast Cancer Study.
PURPOSE Scoring proliferation through Ki67 immunohistochemistry is an important component in predicting therapy response to chemotherapy in patients with breast cancer. However, recent studies have cast doubt on the reliability of "visual" Ki67 scoring in the multicenter setting, particularly in the lower, yet clinically important, proliferation range. Therefore, an accurate and standardized Ki...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 2 شماره
صفحات -
تاریخ انتشار 2016