Expression and prognostic significance of YAP, TAZ, TEAD4 and p73 in human laryngeal cancer
Georgios Tsinias1,2*, Sofia Nikou2*, Nicholas Mastronikolis1, Vasiliki Bravou2 and Helen Papadaki2
1Department of Otolaryngology, Head and Neck Surgery, University General Hospital of Patras and 2Department of Anatomy, Histology and Embryology, University of Patras School of Medicine, Patras, Greece
*Contributed equally
Offprint requests to: Professor Helen Papadaki and Assistant Professor Vasiliki Bravou, Department of Anatomy-Histology-Embryology, University of Patras Medical School, Rion, Patras, 26500, Greece. e-mail: epetrou@upatras.gr and vibra@upatras.gr
Summary. Objectives. The Hippo signaling pathway plays a critical role in organ size control and tissue homeostasis and its perturbation is associated with tumorigenesis. YAP (Yes associated protein) and TAZ (transcriptional co-activator with PDZ- binding motif) are the major nuclear effectors of the Hippo pathway interacting with TEADs (TEA domain) and p73 transcriptional factors to regulate gene expression. Altered expression of the above proteins promotes tumor initiation, progression and metastasis in a variety of cancer types. This study addresses their expression and prognostic significance in human laryngeal carcinoma. Methods. Protein expression of YAP, TAZ, TEAD4 and p73 was examined by immunohistochemistry in 121 human laryngeal squamous cell carcinomas. Correlations with clinicopathological data and survival were evaluated. Results. All proteins were overexpressed in human laryngeal carcinomas compared to non-neoplastic adjacent epithelium. High expression of YAP, TAZ, TEAD4 and p73 correlated significantly with high grade, advanced stage, supraglottic location of tumor, nodal metastases and recurrence. Furthermore, high expression of all proteins was significantly associated with poor overall and disease- free survival. p73 expression proved to be an independent predictive factor of survival and YAP expression proved to be an independent predictive factor of disease recurrence. Conclusions. Deregulation of the expression of the Hippo pathway proteins is implicated in human laryngeal carcinogenesis and YAP and p73 have prognostic significance in the outcome of the disease. Histol Histopathol 35, 983-995 (2020)
Key words: Laryngeal cancer, YAP, TAZ, TEAD4, p73
DOI: 10.14670/HH-18-228