ABSTRACT
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.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Carcinoma, Squamous Cell/metabolism , DNA-Binding Proteins/metabolism , Gene Expression Regulation, Neoplastic , Intracellular Signaling Peptides and Proteins/metabolism , Laryngeal Neoplasms/metabolism , Muscle Proteins/metabolism , Transcription Factors/metabolism , Tumor Protein p73/metabolism , Adaptor Proteins, Signal Transducing/genetics , Adult , Aged , Aged, 80 and over , Carcinogenesis/genetics , Carcinogenesis/metabolism , Carcinogenesis/pathology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , DNA-Binding Proteins/genetics , Female , Humans , Intracellular Signaling Peptides and Proteins/genetics , Laryngeal Neoplasms/genetics , Laryngeal Neoplasms/pathology , Male , Middle Aged , Muscle Proteins/genetics , Prognosis , Signal Transduction/physiology , TEA Domain Transcription Factors , Transcription Factors/genetics , Transcriptional Coactivator with PDZ-Binding Motif Proteins , Tumor Protein p73/genetics , YAP-Signaling ProteinsABSTRACT
Focal adhesion signaling to actin cytoskeleton is critically implicated in cell migration and cancer invasion and metastasis. Actin-binding proteins cofilin and N-WASP regulate actin filament turnover, and focal adhesion proteins parvins and PINCH mediate integrin signaling to the actin cytoskeleton. Altered expression of these proteins has been implicated in human cancer. This study addresses their expression and prognostic significance in human laryngeal carcinoma. Protein expressions of cofilin, N-WASP, α-parvin, ß-parvin, and PINCH1 were examined by immunohistochemistry in 72 human laryngeal squamous cell carcinomas. Correlations with clinicopathological data and survival were evaluated. All proteins examined were overexpressed in human laryngeal carcinomas compared to adjacent nonneoplastic epithelium. High expression of PINCH1 was associated significantly with high grade, lymph node-positive, and advanced stage disease. Moreover, high PINCH1 expression significantly associated with poor overall and disease-free survival and high cytoplasmic PINCH1 expression was shown by multivariate analysis to independently predict poor overall survival. In conclusion, we provide novel evidence that focal adhesion signaling to actin cytoskeleton is implicated in human laryngeal carcinogenesis and PINCH1 has prognostic significance in the disease.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , LIM Domain Proteins/metabolism , Laryngeal Neoplasms/diagnosis , Laryngeal Neoplasms/metabolism , Actin Depolymerizing Factors/metabolism , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Focal Adhesions , Humans , Kaplan-Meier Estimate , Laryngeal Neoplasms/pathology , Male , Membrane Proteins/metabolism , Microfilament Proteins , Middle Aged , Multivariate Analysis , Prognosis , Proportional Hazards Models , Wiskott-Aldrich Syndrome Protein, Neuronal/metabolismABSTRACT
Reconstruction after resection of large tumors of the lower lip requires the use of free flaps in order to restore the shape and the function of the lip, with the free radial forearm flap being the most popular. In this study we describe our experience in using the dorsalis pedis free flap as a salvage option in reconstruction of total lower lip defect in a patient with an extended lower lip carcinoma after failure of the radial forearm free flap, that was initially used. The flap was integrated excellently and on the followup the patient was free of disease and fully satisfied with the aesthetic and functional result.