Correlation of Yes-Associated Protein 1 with Stroma Type and Tumor Stiffness in Hormone-Receptor Positive Breast Cancer.

Abstract

Simple SummaryYAP1 is an oncogene that can be activated by matrix stiffness, as it can act as a mechanotransducer. So far, only in vitro studies regarding YAP1 activation and matrix stiffness are present. We confirmed the activation of YAP1 in breast cancer using human breast cancer tissue and immunohistochemistry. Tumor stiffness was quantified by shear-wave elastography. Nuclear localization of YAP1 showed correlation with tumor stiffness in hormone-receptor positive (HR+) breast cancer. Also, tumors with non-collagen-type stroma showed an association between YAP1 expression and tumor stiffness. YAP1 expression, along with tumor stiffness, may serve as a prognostic candidate in HR+ breast cancer.(1) Background: Yes-associated protein 1 (YAP1) is an oncogene activated under the dysregulated Hippo pathway. YAP1 is also a mechanotransducer that is activated by matrix stiffness. So far, there are no in vivo studies on YAP1 expression related to stiffness. We aimed to investigate the association between YAP1 activation and tumor stiffness in human breast cancer samples, using immunohistochemistry and shear-wave elastography (SWE). (2) Methods: We included 488 patients with treatment-naïve breast cancer. Tumor stiffness was measured and the mean, maximal, and minimal elasticity values and elasticity ratios were recorded. Nuclear YAP1 expression was evaluated by immunohistochemistry and tumor-infiltrating lymphocytes (TILs); tumor-stroma ratio (TSR) and stroma type of tumors were also evaluated. (3) Results: Tumor stiffness was higher in tumors with YAP1 positivity, low TILs, and high TSR and was correlated with nuclear YAP1 expression; this correlation was observed in hormone receptor positive (HR+) tumors, as well as in tumors with non-collagen-type stroma. (4) Conclusions: We confirmed the correlation between nuclear YAP1 expression and tumor stiffness, and nuclear YAP1 expression was deemed a prognostic candidate in HR+ tumors combined with SWE-measured tumor stiffness.