thromboplastin and Mouth-Neoplasms

Accumulating evidence has revealed the role of various components of the coagulatory system in different stages of carcinogenesis including precancerous and initial stages, tumor growth, angiogenesis, stroma generation, and metastasis of malignant cells. This comprehensive review discusses major points of evidence, in addition to recent findings on specific factors associated with the paradigm of oral squamous cell carcinoma. During carcinogenesis, angiogenesis is favored by local conditions of hypoxia, cell-to-cell interactions, and by expression of paracrine growth factors and inflammatory cytokines. In the oral region specifically, genetic association studies have revealed that constitutively high gene expression of certain inflammatory cytokines plays a major role in carcinogenesis. Tissue factor (TF) has a physiological role in hemostasis, but it also constitutes a notable procoagulant in many types of cancer, since it appears to be constitutively expressed by tumor cells. Furthermore, its pathway regulates mechanisms which involve plasmin and matrix metallo-proteinases, both of which seem to be critical in oral carcinogenesis. Thrombin has a central role in hemostasis but it may also promote angiogenesis through pathways independently of fibrin generation. Thrombomodulin may act through attenuation of the tumor-promoting properties of thrombin, but it also may function as a cell-to-cell adhesion molecule, independently of its anticoagulant action. The activation of fibrinogen by thrombin and its cleavage to fibrin monomers result in the rapid formation of fibrin matrix. Furthermore, it is well documented that fibrinogen and cross-linked fibrin reside inside the tumor stroma, facilitating its remodeling, angiogenesis, tumor growth and metastasis. In conclusion, the hemostatic system contributes to the development of the malignant phenotype acting on many different levels.

Topics: Blood Coagulation; Blood Platelets; Hemostasis; Humans; Lipoproteins; Mouth Neoplasms; Neovascularization, Physiologic; Thrombin; Thrombomodulin; Thromboplastin

No clinically approved tumor-specific imaging agents for head and neck cancer are currently available. The identification of biomarkers with a high and homogenous expression in tumor tissue and minimal expression in normal tissue is essential for the development of new molecular imaging targets in head and neck cancer. We investigated the expression of nine imaging targets in both primary tumor and matched metastatic tissue of 41 patients with oral squamous cell carcinoma (OSCC) to assess their potential as targets for molecular imaging. The intensity, proportion, and homogeneity in the tumor and the reaction in neighboring non-cancerous tissue was scored. The intensity and proportion were multiplied to obtain a total immunohistochemical (IHC) score ranging from 0-12. The mean intensity in the tumor tissue and normal epithelium were compared. The expression rate was high for the urokinase-type plasminogen activator receptor (uPAR) (97%), integrin αvβ6 (97%), and tissue factor (86%) with a median total immunostaining score (interquartile range) for primary tumors of 6 (6-9), 12 (12-12), and 6 (2.5-7.5), respectively. For the uPAR and tissue factor, the mean staining intensity score was significantly higher in tumors compared to normal epithelium. The uPAR, integrin αvβ6, and tissue factor are promising imaging targets for OSCC primary tumors, lymph node metastases, and recurrences.

Topics: Humans; Immunohistochemistry; Molecular Imaging; Mouth Neoplasms; Receptors, Urokinase Plasminogen Activator; Squamous Cell Carcinoma of Head and Neck; Thromboplastin; Urokinase-Type Plasminogen Activator

Tumor-specific biomarkers are a prerequisite for the development of targeted imaging and therapy in oral squamous cell carcinoma (OSCC). urokinase-type Plasminogen Activator Receptor (uPAR), Tissue Factor (TF) and Epidermal Growth Factor Receptor (EGFR) are three biomarkers that exhibit enhanced expression in many types of cancers, and have been investigated as potential biomarkers for targeted strategies and prognostication. The aim of the study was to investigate the expression patterns of uPAR, TF and EGFR and their potential prognostic value in OSCC.. Immunohistochemical expression of uPAR, TF and EGFR in tumor resection specimens from 191 patients with primary OSCC was analyzed. Overall (OS) and disease-free survival (DFS) was calculated. Associations between biomarker expression, clinicopathological factors and patient survival was analyzed using the Cox proportional hazards model for univariate and multivariate analysis, log rank and Kaplan-Meier statistics.. uPAR and TF exhibited a highly tumor-specific expression pattern while EGFR also showed expression in normal tissues outside the tumor compartment. The overall positive expression rate of uPAR, TF and EGFR was 95%, 58% and 98%, respectively. High uPAR expression across the entire cohort was negatively associated with OS (p = 0.031, HR = 1.595 (95%CI 1.044-2.439)) in univariate analysis. The 5-year OS for high and low uPAR expression was 39% and 56%, respectively. The expression of TF and EGFR was not associated with survival outcome.. This study may suggest that uPAR and TF could potentially be attractive targets for molecular imaging and therapy in OSCC due to high positive expression rates and tumor-specific expression patterns. High uPAR expression was significantly associated with a reduced survival. uPAR seems to be a prognostic biomarker in oral cancer.

Topics: Adult; Aged; Aged, 80 and over; Apoenzymes; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease-Free Survival; ErbB Receptors; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Mouth Neoplasms; Proportional Hazards Models; Receptors, Urokinase Plasminogen Activator; Thromboplastin; Young Adult