Tumor stiffness measured by shear wave elastography correlates with tumor hypoxia as well as histologic biomarkers in br

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RESEARCH ARTICLE

Open Access

Tumor stiffness measured by shear wave elastography correlates with tumor hypoxia as well as histologic biomarkers in breast cancer Joonghyun Yoo1, Bo Kyoung Seo1* , Eun Kyung Park1, Myoungae Kwon1, Hoiseon Jeong2, Kyu Ran Cho3, Ok Hee Woo4, Sung Eun Song3 and Jaehyung Cha5

Abstract Background: Shear wave elastography (SWE) is an ultrasound technique for the noninvasive quantification of tissue stiffness. The hypoxic tumor microenvironment promotes tumor stiffness and is associated with poor prognosis in cancer. We aimed to investigate the correlation between tumor hypoxia and histologic biomarkers and tumor stiffness measured by SWE in breast cancer. Methods: From June 2016 to January 2018, 82 women with invasive breast cancer who underwent SWE before treatment were enrolled. Average tumor elasticity (Eaverage) and tumor-to-fat elasticity ratio (Eratio) were extracted from SWE. Immunohistochemical staining of glucose transporter 1 (GLUT1) was used to assess tumor hypoxia in breast cancer tissues and automated digital image analysis was performed to assess GLUT1 activities. Spearman correlation and logistic regression analyses were performed to identify associations between GLUT1 expression and SWE values, histologic biomarkers, and molecular subtypes. The Mann–Whitney U test, t test, or Kruskal–Wallis test was used to compare SWE values and histologic features according to the GLUT1 expression (≤the median vs > median). Results: Eaverage (r = 0.676) and Eratio (r = 0.411) correlated significantly with GLUT1 expression (both p < 0.001). Eaverage was significantly higher in cancers with estrogen receptor (ER)–, progesterone receptor (PR)–, Ki67+, and high-grade (p < 0.05). Eratio was higher in cancers with Ki67+, lymph node metastasis, and high-grade (p < 0.05). Cancers with high GLUT1 expression (>median) had higher Eaverage (mean, 85.4 kPa vs 125.5 kPa) and Eratio (mean, 11.7 vs 17.9), and more frequent ER– (21.7% vs 78.3%), PR– (26.4% vs 73.1%), Ki67+ (31.7%% vs 68.3%), human epidermal growth factor receptor 2 (HER2) + (25.0% vs 75.0%), high-grade (28.6% vs 71.4%), and HER2-overexpressing (25.0% vs 75.0%) and triple-negative (23.1% vs 76.9%) subtypes (p < 0.05). Multivariable analysis showed that Eaverage was independently associated with GLUT1 expression (p < 0.001). (Continued on next page)

* Correspondence: [email protected]; [email protected] 1 Department of Radiology, Korea University Ansan Hospital, Korea University College of Medicine, 123 Jeokgeum-ro, Danwon-gu, Ansan-si, Gyeonggi-do 15355, South Korea Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other thir