ABSTRACT
Ductular reaction (DR) is a complex cellular response that occurs in the liver during chronic injuries. DR mainly consists of hyper-proliferative or reactive cholangiocytes and, to a lesser extent, de-differentiated hepatocytes and liver progenitors presenting a close spatial interaction with periportal mesenchyme and immune cells. The underlying pathology of DRs leads to extensive tissue remodeling in chronic liver diseases. DR initiates as a tissue-regeneration mechanism in the liver; however, its close association with progressive fibrosis and inflammation in many chronic liver diseases makes it a more complicated pathological response than a simple regenerative process. An in-depth understanding of the cellular physiology of DRs and their contribution to tissue repair, inflammation, and progressive fibrosis can help scientists develop cell-type specific targeted therapies to manage liver fibrosis and chronic liver diseases effectively.
Subject(s)
Liver Diseases , Humans , Liver Diseases/pathology , Fibrosis , Disease Progression , InflammationABSTRACT
CanAssist Breast (CAB), a prognostic test uses immunohistochemistry (IHC) approach coupled with artificial intelligence-based machine learning algorithm for prognosis of early-stage hormone-receptor positive, HER2/neu negative breast cancer patients. It was developed and validated in an Indian cohort. Here we report the first blinded validation of CAB in a multi-country European patient cohort. FFPE tumor samples from 864 patients were obtained from-Spain, Italy, Austria, and Germany. IHC was performed on these samples, followed by recurrence risk score prediction. The outcomes were obtained from medical records. The performance of CAB was analyzed by hazard ratios (HR) and Kaplan Meier curves. CAB stratified European cohort (n = 864) into distinct low- and high-risk groups for recurrence (P < 0.0001) with HR of 3.32 (1.85-5.93) like that of mixed (India, USA, and Europe) (n = 1974), 3.43 (2.34-4.93) and Indian cohort (n = 925), 3.09 (1.83-5.21). CAB provided significant prognostic information (P < 0.0001) in women aged ≤ 50 (HR: 4.42 (1.58-12.3), P < 0.0001) and >50 years (HR: 2.93 (1.44-5.96), P = 0.0002). CAB had an HR of 2.57 (1.26-5.26), P = 0.01) in women with N1 disease. CAB stratified significantly higher proportions (77%) as low-risk over IHC4 (55%) (P < 0.0001). Additionally, 82% of IHC4 intermediate-risk patients were stratified as low-risk by CAB. Accurate risk stratification of European patients by CAB coupled with its similar performance inIndian patients shows that CAB is robust and functions independent of ethnic differences. CAB can potentially prevent overtreatment in a greater number of patients compared to IHC4 demonstrating its usefulness for adjuvant systemic therapy planning in European breast cancer patients.
