thromboplastin and Squamous-Cell-Carcinoma-of-Head-and-Neck

Elevated tissue factor (TF) expression, although restricted in normal tissue, has been reported in multiple solid cancers, and expression has been associated with poor prognosis. This manuscript compares TF expression across various solid tumor types via immunohistochemistry in a single study, which has not been performed previously.. To increase insight in the prevalence and cellular localization of TF expression across solid cancer types, we performed a detailed and systematic analysis of TF expression in tumor tissue obtained from patients with ovarian, esophageal, bladder, cervical, endometrial, pancreatic, prostate, colon, breast, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and glioblastoma. The spatial and temporal variation of TF expression was analyzed over time and upon disease progression in patient-matched biopsies taken at different timepoints. In addition, TF expression in patient-matched primary tumor and metastatic lesions was also analyzed.. TF expression was detected via immunohistochemistry (IHC) using a validated TF-specific antibody. TF was expressed in all cancer types tested, with highest prevalence in pancreatic cancer, cervical cancer, colon cancer, glioblastoma, HNSCC, and NSCLC, and lowest in breast cancer. Staining was predominantly membranous in pancreatic, cervical, and HNSCC, and cytoplasmic in glioblastoma and bladder cancer. In general, expression was consistent between biopsies obtained from the same patient over time, although variability was observed for individual patients. NSCLC biopsies of primary tumor and matched lymph node metastases showed no clear difference in TF expression overall, although individual patient changes were observed.. This study shows that TF is expressed across a broad range of solid cancer types, and expression is present upon tumor dissemination and over the course of treatment.

Topics: Carcinoma, Non-Small-Cell Lung; Female; Glioblastoma; Head and Neck Neoplasms; Humans; Lung Neoplasms; Male; Squamous Cell Carcinoma of Head and Neck; 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

The clinical introduction of molecular imaging for the management of oropharyngeal squamous cell carcinoma (OPSCC) relies on the identification of relevant cancer‑specific biomarkers. The application of three membrane‑bound receptors, namely urokinase‑type plasminogen activator receptor (uPAR), tissue factor (TF) and EGFR have been previously explored for targeted imaging and therapeutic strategies in a broad range of solid cancers. The present study aimed to investigate the expression patterns of uPAR, EGFR and TF by immunohistochemistry (IHC) to evaluate their potential for targeted imaging and prognostic value in OPSCC. In a retrospective cohort of 93 patients with primary OPSCC, who were balanced into the 45 human papillomavirus (HPV)‑positive and 48 HPV‑negative groups, the IHC‑determined expression profiles of uPAR, TF and EGFR in large biopsy or tumor resection specimens were analyzed. Using the follow‑up data, overall survival (OS) and recurrence‑free survival were measured. Specifically, associations between survival outcome, biomarker expression and clinicopathological factors were examined using Cox proportional hazards model and log‑rank test following Kaplan‑Meier statistics. After comparing the expression pattern of biomarkers within the tumor compartment with that in the adjacent normal tissues, uPAR and TF exhibited a highly tumor‑specific expression pattern, whereas EGFR showed a homogeneous expression within the tumor compartment as well as a consistent expression in the normal mucosal epithelium and salivary gland tissues. The positive expression rate of uPAR, TF and EGFR in the tumors was 98.9, 76.3 and 98.9%, respectively. No statistically significant association between biomarker expression and survival outcome could be detected. Higher uPAR expression levels had a trend towards reduced OS according to results from univariate analysis (P=0.07; hazard ratio=2.01; 95% CI=0.92‑4.37). Taken together, these results suggest that uPAR, TF and EGFR may be suitable targets for molecular imaging and therapy in OPSCC. In particular, uPAR may be an attractive target owing to their high positive expression rates in tumors and a highly tumor‑specific expression pattern.

Topics: Biomarkers, Tumor; ErbB Receptors; Humans; Molecular Imaging; Molecular Targeted Therapy; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prognosis; Receptors, Urokinase Plasminogen Activator; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Thromboplastin

: Microvesicles associated with tissue factor (TF) may play a role in cancer-related venous thromboembolism; however, not much is known about their interaction with the tumour stroma, especially the endothelium or any procoagulant changes seen because of this interaction. Using a head and neck squamous cell carcinoma line (UMSCC81B) and human umbilical vein endothelial cells (HUVECs), this study explored the interaction of cancer microvesicles released into cell culture media with endothelial cells in vitro, and assessed the procoagulant activity resulting from this interaction. Cell-free media containing UMSCC81B cancer microvesicles supported coagulation in a concentration-dependent manner, suggesting TF and microvesicle presence, this media was then added to HUVECs and flow cytometry analysis showed a subpopulation of HUVECs that had acquired a significantly high expression of TF, which was dependent upon the concentration of UMSCC81B media containing microvesicles present and confocal microscopy confirmed HUVECs associated with labelled microvesicles. The range of TF-positive HUVECs was determined to be 0, 4.2(±1.4), 12.5(±3.72), and 45.9(±18.7)% for microvesicle-positive media concentration of 0, 25, 50, and 100%, respectively, which resulted in decreasing prothrombin values of more than 600 (no clot), 126.4, 65.8, and 47.8 s. Our results demonstrate that procoagulant microvesicles shed by UMSCC81B induced a procoagulant effect in HUVECs through increased clotting activity and cell membrane surface expression of TF.

Topics: Blood Coagulation; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell-Derived Microparticles; Endothelial Cells; Endothelium, Vascular; Head and Neck Neoplasms; Human Umbilical Vein Endothelial Cells; Humans; Squamous Cell Carcinoma of Head and Neck; Thromboplastin; Venous Thromboembolism