thromboplastin and Breast-Diseases

The association between cancer and thromboembolic disease has been known for over a century. Increased tissue factor expression by endothelial cells, monocytes or macrophages is implicated. Thus, monocyte tissue factor measurements may reflect disease presence or progression.. Using a 2 stage kinetic chromogenic assay, monocyte tissue factor levels were assessed in normal controls (n=60), patient controls (hernia or cholecystectomy, n=60) and in patients with benign and malignant disease of the bladder (n=73), prostate (n=81), breast (n=83) and colorectum (n=62). This was performed as baseline (resting cells) and after 6 hours incubation with (stimulated) and without (unstimulated) lipopolysaccharide. Each benign disease group was sub-divided into inflammatory and non-inflammatory categories.. The relative operating characteristic curve for the lipopolysaccharide-stimulated monocyte tissue factor assay showed sensitivity and specificity for cancer, the area under the curve being 0.71. The control groups and the benign non-inflammatory groups gave similar results and were pooled for further analysis. Each malignant group showed higher monocyte tissue factor levels than the control groups for baseline (P< 0.05) and lipopolysaccharide-stimulated cells (P< 0.05). All benign inflammatory groups apart from breast, showed increased monocyte tissue factor levels over controls for baseline (P< 0.05) and lipopolysaccharide-stimulated cells (P< 0.05). In all cases there was no significant difference between the malignant and the benign inflammatory groups. Monocyte tissue factor levels were related to tumor grade or stage, patients' survival time, serum prostate specific antigen and static bone scan images. Levels were also higher in patients with bladder cancer recurrence and in those who subsequently died.. Lipopolysaccharide-stimulated monocyte tissue factor assay showed sensitivity and specificity for cancer compared to controls. Monocyte tissue factor levels are raised in malignant groups compared to controls and non-inflammatory diseases but not when compared with inflammatory conditions. Stimulated cells give better discrimination between the groups and may be useful in identifying high risk individuals. Monocyte tissue factor levels were related to tumor progression.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Diseases; Breast Neoplasms; Case-Control Studies; Colonic Diseases; Colorectal Neoplasms; Discriminant Analysis; Disease Progression; Female; Humans; Inflammation; Male; Middle Aged; Monocytes; Prostatic Diseases; Prostatic Neoplasms; Risk Factors; Sensitivity and Specificity; Thromboembolism; Thromboplastin; Urinary Bladder Diseases; Urinary Bladder Neoplasms

Activation of blood coagulation is a common complication of cancer in man and experimental animals. The causes of such activation may be multifactorial, but increased production of tissue factor (TF) by the host mononuclear cells may be involved. TF is not only produced by human monocytes (mTF) and tumour cells, but is also found in urine (uTF), where measurements might be clinically important. Using a highly reproducible (intra-assay CV 2.3 per cent and inter-assay CV 8.1 per cent) one-stage kinetic chromogenic assay (KCA) developed by this group, uTF levels were measured in controls [healthy volunteers (n = 57), patients with renal stones and a normal ESR (n = 30)] and in patients with benign and malignant diseases of the breast (n = 94) and large bowel (n = 62). Each benign disease group was sub-divided into inflammatory and non-inflammatory categories. There were no significant differences between the controls and the benign non-inflammatory groups, so they were unified for further analysis. Malignant groups, irrespective of tumour types, showed significantly higher uTF levels than controls (p < 0.001 for breast and p < 0.01 for large bowel). Similarly, breast and colorectal benign inflammatory groups showed significant increases over controls (p < 0.01 and p < 0.001, respectively). Patients with malignant disease showed uTF activity above the upper quartile range of the normal control group for breast, 77.3 per cent, and large bowel, 73 per cent. uTF levels were related to histological tumour grading and were higher in non-surviving patients. In conclusion, uTF levels are raised in malignant and inflammatory disease compared with controls and patients with non-inflammatory conditions. uTF levels may reflect tumour progression.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Diseases; Breast Neoplasms; Child; Child, Preschool; Colorectal Neoplasms; Diagnosis, Differential; Female; Humans; Kidney Calculi; Male; Middle Aged; Neoplasm Proteins; Survival Rate; Thromboplastin

Hypercoagulability in malignant disease can be attributed, in part, to excess generation of tissue factor (thromboplastin) by the monocyte. Incubation of anticoagulated venous blood with endotoxin (a cellular activator) enables the generation of tissue factor by monocytes. The quantity of this procoagulant generated is determined by a simple recalcification time (a marker for cellular activation). Individuals with breast cancer have significantly shorter endotoxin-activated recalcification times than patients with cystic hyperplasia, who have, in turn, significantly reduced recalcification times when compared with those of healthy volunteers.

Topics: Adult; Breast Diseases; Breast Neoplasms; Female; Fibrocystic Breast Disease; Humans; Middle Aged; Thromboplastin