Tissue factor (TF) and factor VII/TF ratio (fVIIa:TF) as potential indicators of malignancy in pancreatic cystic lesions.

Abstract

669 Background: Premalignant pancreatic cellular genotype may remain stable for many years, but compounding conditions can produce rapid malignant cellular transformation. This onset is rarely spontaneous and is often associated with the presence of inflammation. One inflammatory modulator is “tissue factor (TF),” which usually acts in complex with “coagulation factor VIIa (fVIIa)” to initiate coagulation. The role of TF in malignancy and its impact beyond thrombosis on cell proliferation, angiogenesis, and metastasis is well established. This suggests that TF may be a diagnostic marker in the inflammatory microenvironment of the precursor lesions of pancreatic cancer. Aim: To examine the potential of TF concentrations and the fVII:TF ratio within pancreatic cyst fluid as indicators of malignant cellular transformation from benign to malignant. Methods: Cyst fluid was prospectively collected from 31 patients with pancreatic cystic lesions (REC 18/LO/0736) and analysed in a blinded fashion. The level of TF and fVIIa proteins were measured by ELISA, and the fVIIa:TF ratios calculated. A cut-off value for TF concentration was determined using a ROC curve and compared to the conventional assessment parameters, including radiological features, carcinoembryonic antigen (CEA) and amylase. Results: Patients were categorised into four groups based on histology. Significant histological stage-dependent increases in TF level were observed, which corresponded to the progression of the normal ductal epithelium to invasive adenocarcinoma. The mean TF concentration was significantly higher ( p= 0.006) in the high-risk group (high-grade dysplasia & malignant; 1.17 ng/ml, 95% CI 0.68, 1.67) vs the low-risk group (benign & low-grade dysplasia; 0.27 ng/ml, 95% CI 0.1, 0.44). A strong positive correlation between TF concentration and the high-risk group was observed (correlation coefficient 0.746, p < 0.001, the cut-off value for TF 0.75 ng/ml, AUC 0.877, p= 0.002). In addition, the fVIIa:TF ratio, was marginally lower ( p= 0.274) in the high-risk group (mean = 84.82 [95% CI 0, 185.04]) vs the low-risk group (mean = 437.46 [95% CI 0, 901.02]). TF concentrations performed consistently better as an indicator of malignant transformation when compared to the conventional parameters and will be presented at the meeting. Conclusions: Cyst-associated TF levels appear to correlate with the cytological progression to the malignant phenotype, while the fVIIa:TF ratio indicates a breakdown in the ability of the body to contain the disease. Such indicators may allow better presurgical discrimination of malignant potential of tumours and offer a more nuanced tool for monitoring indeterminate cystic lesions. Further work is needed with a larger cohort to confirm these findings.