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

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). Conclusions Tumor stiffness on SWE is significantly correlated with tumor hypoxia as well as histologic biomarkers. In particular, Eaverage on SWE has independent prognostic significance for tumor hypoxia in the multivariable analysis and can potentially be used as a noninvasive imaging biomarker to predict prognosis and pretreatment risk stratification in breast cancer patients.

Is There a Correlation between Multiparametric Assessment in Ultrasound and Intrinsic Subtype of Breast Cancer?

“…Yoo et al showed that increased (mean) tumor stiffness in SWE imaging is correlated with hypoxia of the tumor and surrounding tissues (assessed using expression of an endogenous GLUT1 protein) and is an independent prognostic biomarker. Increased stiffness is associated with adverse prognosis [27]. The highest stiffness was found in TNBC tumors (13/82) in this study.…”

Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment

“…In the first place, many preclinical models do not always reproduce the carcinoma structure found in their respective human tumors. Another important feature of human solid tumors, often absent in mouse tumor models, is their considerable higher stiffness compared to their neighboring healthy tissues which is highly correlated with cancer progression and metastasis (23,24,47,48). These two features can often be found in human xenograft models that, on the other hand, are not suitable to study immune reactions.…”

The Advance of Magnetic Resonance Elastography in Tumor Diagnosis

“…Changes in the elasticity and stiffness of human tissues reflect the pathological development process to a certain extent (22). For example, 80-90% of patients with liver cirrhosis will develop liver cancer, with tumor stiffness directly related to tumor grade (23)(24)(25). In addition, high tumor stiffness hinders the effective delivery of anti-cancer drugs in the body (26)(27)(28).…”

“…The sensitivity of MRE in distinguishing between severe and mild liver fibrosis is 98%. The increase in liver stiffness in patients with liver cirrhosis is an important risk factor for developing hepatocellular carcinoma (HCC) ( 24 ).…”