thromboplastin and Esophageal-Neoplasms

It has been suggested that the blood clotting initiator protein, tissue factor (TF), participates in tumor growth, metastasis and angiogenesis. In addition, a family of G protein-coupled-receptors known as protease-activated receptors (PARs) has also been implicated in tumor biology. These receptors might be activated by blood coagulation proteases thus eliciting a number of pro-tumoral responses, including the expression of interleukin-8 (IL-8). Therefore, in this study we analyzed the expression of TF, PAR-1, PAR-2 and IL-8 genes in patients with esophageal cancer, one of the most aggressive neoplastic diseases. Total RNA was extracted from tissue samples (tumor and the corresponding normal mucosa) obtained from patients submitted to esophagectomy or endoscopy and further analyzed by semi-quantitative reverse transcriptase-polymerase (RT-PCR) and/or real-time quantitative PCR (qPCR). Expression of full-length transmembrane TF was significantly higher in tumor samples whereas no differences were observed in alternatively spliced TF transcripts. Tumor tissue showed increased mRNA levels for PAR-1 but not PAR-2. Remarkably, IL-8 expression was not detected in most normal tissues but showed very high expression in tumor samples. As expected, qPCR revealed greater differences in the expression pattern of all transcripts analyzed but the general profile was very similar to that observed by RT-PCR. Altogether our data suggest a possible role for blood clotting proteins in the biology of human esophageal cancer.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Brazil; Esophageal Neoplasms; Esophagectomy; Esophagoscopy; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Male; Middle Aged; Receptor, PAR-1; Receptor, PAR-2; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Thromboplastin; Up-Regulation

Neoadjuvant chemotherapy (NACT) improves the prognosis of patients with esophageal cancer who respond, but it is not effective in nonresponders. Therefore, it is crucial to establish a reliable method of predicting response before initiation of chemotherapy. Hypercoagulability, which is thought to be because of upregulation of tissue factor (TF) in cancer cells, was reported to be associated with chemoresistance. The aim of this study was to investigate the association between TF expression and response to NACT in esophageal cancer.. In 67 patients with advanced esophageal cancer, TF expression in pretreatment biopsy samples was evaluated immunohistochemically and correlated with clinicopathologic factors and response to chemotherapy.. TF was expressed by 43.3% of the tumors, but there were no correlations observed with any clinicopathologic parameters examined. Clinical and histologic responses to chemotherapy were significantly worse in TF-positive patients compared with TF-negative patients. Multivariate analysis revealed that TF expression was significantly associated with a poor clinical response (P = 0.0431). TF expression was also independently associated with poor progression-free survival (P = 0.0353).. TF expression levels in pretreatment biopsy samples are useful for predicting response to NACT in advanced esophageal cancer. Further studies of mechanisms underlying the relationship between TF expression and chemosensitivity are needed.

Topics: Aged; Biopsy; Carcinoma, Squamous Cell; Disease Progression; Disease-Free Survival; Drug Resistance, Neoplasm; Esophageal Neoplasms; Esophagus; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Predictive Value of Tests; Prognosis; Thrombophilia; Thromboplastin

It has been demonstrated that tissue factor (TF) may be involved in the tumor-derived procoagulatory status and angiogenic modulation in certain solid tumors. In the present study, we examined immunohistochemical localisation of TF in esophageal squamous cell carcinomas (ESCC) from 103 patients. TF immunopositivity was found in 91.3% of all tumor sections, while normal esophageal tissues were immunonegative. Patients were divided into a low TF immunoreactivity group (9 cases of negative and 48 cases of weak positive) and a high TF immunoreactivity group (35 cases of moderate positive and 11 cases of strong positive). TF immunoreactivity was significantly correlated to the presence of distant metastasis (P=0.0014), while it was not correlated to patient's gender, age, tumor size, depth of tumor invasion or lymph node metastasis. Survival analysis revealed that the overall survival rate in the patients that had high TF immunoreactivity was significantly poorer than those with low TF immunoreactivity (P=0.0094). Univariate analysis demonstrated that tumor size (P=0.0095), depth of tumor invasion (P=0.0050), lymph node metastasis (P=0.0045) and distant metastasis (P<0.0001) were effective predictors of prognosis in patients. However, only distant metastasis could independently predict patients' outcomes by the analysis of multivariate proportional hazards regression (P=0.0043). Furthermore, the intratumoral microvessel density (MVD), evaluated by CD34 immunolabeling, indicated that MVD was positively correlated to the TF immunoreactivity (P=0.0056). It is concluded that TF immunopositivity in ESCC tissues is strongly correlated to the intratumoral angiogenesis and to poor patient prognosis.

Topics: Adult; Age Factors; Aged; Antigens, CD34; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Hemostatics; Humans; Lymphatic Metastasis; Male; Microvessels; Middle Aged; Multivariate Analysis; Neovascularization, Pathologic; Proportional Hazards Models; Sex Factors; Survival Analysis; Thromboplastin

The cancer procoagulant (CP) activity has been evaluated in homogenates of stomach and esophagus cancer tissues and in patients serum. Activity of CP in homogenates of stomach and esophagus cancer tissues as well as in serum of examined cancer patients were statistically higher than in the control group. The data indicate that estimation of CP activity in the neoplasmic tissues homogenates and in serum may be suggested as an new biochemical marker of cancer process useful in oncological diagnosis.

Topics: Adult; Aged; Biomarkers, Tumor; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Reference Values; Stomach Neoplasms; Thromboplastin

Topics: Anticoagulants; Blood Coagulation Factors; Blood Coagulation Tests; Esophageal Neoplasms; Factor VII; Fibrinogen; Heparin; Humans; Postoperative Complications; Prothrombin; Stomach Neoplasms; Thromboembolism; Thromboplastin