Standardized Ki67 Diagnostics Using Automated Scoring—Clinical Validation in the GeparTrio Breast Cancer Study

Abstract

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 Ki67 scoring is pivotal both in routine diagnostics and larger multicenter studies.Experimental Design: We validated a novel fully automated Ki67 scoring approach that relies on only minimal a priori knowledge on cell properties and requires no training data for calibration. We applied our approach to 1,082 breast cancer samples from the neoadjuvant GeparTrio trial and compared the performance of automated and manual Ki67 scoring.Results: The three groups of autoKi67 as defined by low ( 15%), medium (15.1%-35%), and high (>35%) automated scores showed pCR rates of 5.8%, 16.9%, and 29.5%, respectively. AutoKi67 was significantly linked to prognosis with overall and progression-free survival P values P OS < 0.0001 and P PFS < 0.0002, compared with P OS < 0.0005 and P PFS < 0.0001 for manual Ki67 scoring. Moreover, automated Ki67 scoring was an independent prognosticator in the multivariate analysis with P OS ¼ 0.002, P PFS ¼ 0.009 (autoKi67) versus P OS ¼ 0.007, P PFS ¼ 0.004 (manual Ki67).Conclusions: The computer-assisted Ki67 scoring approach presented here offers a standardized means of tumor cell proliferation assessment in breast cancer that correlated with clinical endpoints and is deployable in routine diagnostics. It may thus help to solve recently reported reliability concerns in Ki67 diagnostics.

Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer

“…1G). To confirm the change in proliferation status of tumors, xenografts were stained for Ki67, which is used clinically to assess the proliferative fraction in breast cancer (22). All control xenografts displayed stronger Ki67 staining than that of ivermectin-treated mice (Fig.…”

The region-of-interest size impacts on Ki67 quantification by computer-assisted image analysis in breast cancer

“…Several commercial applications have been developed or adopted for CAIA-based Ki67 quantification. As a fully automated, solely computer-based detection of the tumor cell compartment raises questions regarding the diagnostic responsibility [26][27][28], many of these commercial applications rely on a measurement in a single, user-defined region of interest (ROI) [18,[29][30][31]. However, because of intratumoral proliferative heterogeneity, definition of the ROI, in terms of size and location, remains an important step in the analytical procedure [20].…”

Self‐Stabilized Hyaluronate Nanogel for Intracellular Codelivery of Doxorubicin and Cisplatin to Osteosarcoma

“…Ki‐67 was a nuclear marker for indicating cell proliferation, and also demonstrated as an optimal proliferation antigen for assessing the prognosis of cancer patients 22. The expression of Ki‐67 was measured in tumor sections to further evaluate the tumor apoptosis by immunohistochemistry.…”