thromboplastin and Adenoma

Tissue factor (TF) expression in human cancers has been associated with a procoagulant state and facilitation of metastasis. This study was conducted in order to evaluate if TF was expressed in canine mammary tumours. Forty epithelial mammary tumours from 28 dogs were included. TF expression of the tumours was evaluated by immunohistochemistry using a polyclonal antibody against recombinant canine TF. In addition, thromboelastography, haemostatic and inflammatory parameters were evaluated in the patients. TF was recognized in 44% of benign and 58% of malignant tumours. TF localized to the cytoplasmic membrane of neoplastic luminal epithelial cells and/or diffusely in the cytoplasm. No association was found between TF expression and stage or grade of disease. A significant association between TF expression and antithrombin and plasminogen was found, and extensive TF expression was seen in a lymph node metastasis classified as anaplastic mammary carcinoma from a dog with concomitant disseminated intravascular coagulation (DIC).

Topics: Adenoma; Animals; Antithrombins; Biomarkers, Tumor; Blood Coagulation; Carcinoma; Dog Diseases; Dogs; Female; Gene Expression Regulation, Neoplastic; Inflammation; Mammary Neoplasms, Animal; Neoplasm Grading; Neoplasm Staging; Plasminogen; Thromboplastin

Colorectal cancer (CRC) is a major cause of morbidity and mortality, and the composition of the tumour stroma is a strong predictor of survival in this cancer type. Tissue factor (TF) functions as the trigger of haemostasis together with its ligand coagulation factor VII/VIIa, and TF expression has been found in tumour cells of colorectal tumours. However, TF expression in the CRC tumour stroma or its relationship to patient outcome has not yet been studied. To address this question we developed and validated a specific anti-TF antibody using standardised methods within the Human Protein Atlas project. We used this antibody to investigate TF expression in normal colorectal tissue and CRC using immunofluorescence and immunohistochemistry in two patient cohorts. TF was strongly expressed in a cell population immediately adjacent to the colorectal epithelium. These TF-positive cells were ACTA2-negative but weakly vimentin-positive, defining a specific population of pericryptal sheath cells. In colorectal tumours, TF-positive sheath cells were progressively lost after the adenoma-to-carcinoma transition, demonstrating downregulation of this source of TF in CRC. Furthermore, loss of sheath cell TF was significantly associated with poor overall and disease-specific survival in rectal but not colon cancers. In conclusion, we demonstrate that TF is a marker of a specific cell population in the large intestine, which is lost during CRC progression. Our results highlight the role of the tumour stroma in this cancer type and suggest TF to be a potential prognostic biomarker in rectal cancers through the identification of pericryptal sheath cells.

Topics: Adenoma; Aged; Aged, 80 and over; Carcinoma; Colorectal Neoplasms; Disease Progression; Female; Humans; Immunohistochemistry; Intestine, Large; Male; Middle Aged; Stromal Cells; Thromboplastin

Tissue factor (TF), which has a role in normal tissue haemostasis, was reported to be aberrantly expressed, associated with higher microvascular density and a poor prognosis in intestinal-type gastric adenocarcinoma in the Japanese population. This is the first study to look at the relationship of TF and the metaplasia-adenoma-carcinoma sequence (MACS) of gastric cancer in a European population.. The expression of TF was examined immunohistochemically in 191 gastric tissue samples: (13: normal; 18: intestinal metaplasia; 160: gastric adenocarcinoma) from the European population.. TF was not expressed in normal gastric mucosal cells. A strong intensity of staining was found in intestinal metaplasia cells but in 2 of 18 samples. TF expression increased with advancing stage of gastric cancer (P<0.0001, Jonckheere's test for ordered medians). Stage 3-4 gastric cancers preferentially expressed TF (34%, P=0.04). In comparison with the Japanese study, TF was not expressed at a higher level in intestinal vs diffuse-type gastric cancers and expression had 'no prognostic' significance.. TF may be involved in tumour progression along the MACS of gastric cancer in the European population and is shown to start in precancerous lesions. However, clinical features may differ due to differences in biological features in the two populations, as reflected by differences in TF expression profile.

Topics: Adenocarcinoma; Adenoma; Adult; Aged; Aged, 80 and over; Carcinoma; Disease Progression; Female; Gastric Mucosa; Humans; Immunohistochemistry; Male; Metaplasia; Middle Aged; Prognosis; Stomach; Stomach Neoplasms; Thromboplastin; White People

The aim of this study was to examine the relationship between tissue factor (TF), vascular endothelial growth factor (VEGF) and the onset of angiogenesis in the adenoma-carcinoma sequence (ACS), the stepwise process encompassing colorectal cancer (CRC) disease progression.. 210 surgical specimens comprising the ACS were immunohistochemically stained for endothelial cells (CD31), VEGF and TF. Angiogenesis quantified using Chalkley grid analysis (microvascular density; MVD), and VEGF/TF expression were semiquantitatively graded and correlated with standard prognostic indicators including 5 year follow-up. VEGF and TF were measured by ELISA in tumour specimens and normal mucosa from an additional 90 CRC patients.. There was a significant increase in MVD across the ACS (p < 0.0005) with significant correlations with Dukes' stage (p = 0.01) and lymph node involvement (p = 0.02). The greatest increase in MVD was related to the onset of dysplasia, with an associated significant increase in VEGF expression (p < 0.0005). There was a significant relationship between VEGF and TF expression in the initial phase of the ACS (k = 0.44, p < 0.005), although no correlation between VEGF or TF, and MVD, tumour size, Dukes' classification, lymph node involvement or survival was found.. These findings are the first to suggest that the angiogenic switch occurs at the onset of dysplasia in the ACS, and provide further evidence of the close association between VEGF and TF in the early stages of CRC development.

Topics: Adenocarcinoma; Adenoma; Adult; Aged; Aged, 80 and over; Colorectal Neoplasms; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Male; Middle Aged; Neoplasm Proteins; Neovascularization, Pathologic; Survival Analysis; Thromboplastin; Vascular Endothelial Growth Factor A

To investigate the correlation between tissue factor (TF) expression and hepatic metastasis and prognosis in rectal cancer.. TF expression was retrospectively studied by immunohistochemical method in specimens of 40 rectal cancer, 3 hepatic metastasis and 6 benign adenoma with relation to their clinicopathologic data.. 1. TF expression was detected in 20 (50%) of the 40 primary rectal cancer specimens and all the 3 hepatic metastatic specimens, but not in the 6 benign adenoma or normal mucosa of rectum, 2. Significant correlation was observed between TF expression and synchronic hepatic metastasis (P = 0.002) and heterochronic hepatic metastasis (P = 0.001) and 3. TF was a risk factor for the prognosis of primary rectal cancer (P = 0.024).. Tissue factor expression may play a role in the process of developing hepatic metastasis. It may be considered as a new clinical indicator for monitor of hepatic metastasis and prognosis of primary rectal cancer.

Topics: Adenoma; Humans; Immunohistochemistry; Liver Neoplasms; Logistic Models; Predictive Value of Tests; Proportional Hazards Models; Rectal Neoplasms; Rectum; Retrospective Studies; Staining and Labeling; Thromboplastin

Topics: Adenoma; Biomarkers, Tumor; Humans; Intestinal Neoplasms; Intestine, Large; Male; Neoplasms; Prognosis; Prostatic Neoplasms; Thromboplastin

Tissue factor (TF) was initially identified as an important factor in the initiation of coagulation. TF has recently been found to be expressed highly in certain types of malignant tumors. It has also been reported to be involved in systemic coagulopathy in cancer patients and in the proliferative and invasive activities of tumor cells. Tissue factor pathway inhibitor (TFPI) is a strong biologic inhibitor of TF. To the authors' knowledge, this is the first study of the expression of TF and TFPI in human pituitary adenoma.. The expression of TF and TFPI were analyzed by immunohistochemical methods in human pituitary adenoma samples. To examine whether TF and TFPI expression influence the proliferative and/or invasive character of pituitary adenomas, the authors determined the MIB-1 labeling indices and invasiveness of all the pituitary adenomas they examined. Furthermore, to determine whether TF contributes to coagulation inside adenoma tissues, the incidence of cysts or hematomas in adenomas was analyzed.. In cells from 29 of 83 pituitary adenomas, overexpression of TF was observed. This was not the case for normal pituitary gland cells. TFPI was not expressed in either the adenomas or the normal pituitary glands from adenoma-bearing individuals. The expression of TF was significantly correlated with the formation of cysts or hematomas in pituitary adenomas. However, no such correlation with either the proliferative activity or the invasive character of the adenomas was observed.. Locally overexpressed TF in adenoma cells may contribute to the development of vascular events, such as infarction and/or hemorrhagic infarction, in pituitary adenomas.

Topics: Adenoma; Adult; Aged; Cysts; Female; Hematoma; Humans; Infarction; Lipoproteins; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Thromboplastin

Generation of thromboplastin by monocytes has been shown to play a vital role in hypercoagulable states seen in malignancy. The purpose of this study was to compare the procoagulant activity in cancer patients and controls. Recalcification times (RT) of whole blood from 19 normal volunteers, 8 patients with benign polyps, 12 patients previously treated by surgery for head and neck (H&N) or colon cancer, and 13 untreated patients with various stages of H&N or colon cancer were determined. Tests were performed with and without stimulation with Escherichia coli endotoxin. The mean RT in saline (RTS) of untreated patients with early cancer (4.58 +/- 0.83 min) and that of patients with advanced cancer (5.23 +/- 1.16 min) were lower than that of controls (6.55 +/- 0.82 min), P less than 0.01 and P less than 0.05, respectively. The RTS of patients previously treated and of those with benign polyps were no different from those of controls. Activation with endotoxin significantly lowered the recalcification times (RTE) in the early (3.90 +/- 0.58 min) and advanced cancer patients (4.23 +/- 0.66 min) compared to the RTE of controls (5.69 +/- 0.75 min, P less than 0.01 for both groups) as well as compared to those with benign tumors, P less than 0.05. The mean RTE of previously treated patients (4.72 +/- 0.58 min) was also lower than that of controls, P less than 0.05. Our results suggest that RT is significantly reduced in cancer patients compared to that of controls. Furthermore, monocyte activation with endotoxin may enable us to distinguish cancer patients from controls as well as from those with benign tumors.

Topics: Adenoma; Adult; Blood Coagulation Tests; Carcinoma, Squamous Cell; Colonic Neoplasms; Head and Neck Neoplasms; Humans; Male; Middle Aged; Monocytes; Neoplasms; Thromboplastin

Topics: Adenoma; Antithyroid Agents; Drug Synergism; Fibrinolysis; Goiter; Hematoma; Hemorrhage; Humans; Plasminogen; Postoperative Complications; Preoperative Care; Thromboplastin; Thyroid Gland; Thyroid Neoplasms