Anti-Human TFPI2 Polyclonal Antibody

The aim of this study was to investigate tissue factor (TF) and its inhibitors TFPI and TFPI2 in secretory endometrium of fertile women and in women with unexplained infertility in relation to endometrial receptivity. In addition, common variation in the regulatory area of TF and TFPI genes was studied. Immunostaining of TF and TFPI, together with the appearance of pinopodes, revealed similar expression pattern in fertile endometrium throughout the secretory phase, being highest at the time of implantation. When compared protein expression levels at the time of implantation, infertile women demonstrated significantly higher TFPI expression in luminal epithelium. Furthermore, polymorphism TF -603 A/G was associated with the endometrial protein level in infertile women, being highest in women with GG genotype, and variation TFPI -287 T/C was associated with unexplained infertility, where infertile women presented more frequently T allele than fertile women. Contrary to TF and TFPI, TFPI2 showed different mRNA and protein expression patterns in fertile endometrium, and no differences between fertile and infertile women were detected. We conclude that the TF pathway is involved in normal endometrial maturation, where TF and TFPI seem to have important roles at the time of embryo implantation. Higher TFPI expression level during the time of embryo implantation and TFPI -287 T allele could be risk factors for unexplained infertility. No distinct involvement of TFPI2 in the regulation of endometrial receptivity and unexplained infertility was found.

Ductal adenocarcinoma of the pancreas is the fourth leading cause of cancer death and is usually diagnosed late. Intraductal papillary mucinous neoplasms are an increasingly recognized precursor to invasive ductal adenocarcinoma of the pancreas. Identifying the alterations in DNA methylation that arise during intraductal papillary mucinous neoplasm development may facilitate the development of markers that could be used to differentiate intraductal papillary mucinous neoplasms from non-neoplastic pancreatic cystic lesions. Surgically resected intraductal papillary mucinous neoplasms and adjacent ductal adenocarcinomas were microdissected from 50 patients. Normal pancreas was also obtained from 27 patients with intraductal papillary mucinous neoplasms or pancreatic adenocarcinomas and 10 patients with well-differentiated pancreatic endocrine neoplasms. Methylation-specific PCR was performed on isolated DNA for seven genes (SPARC, SARP2, TSLC1, RELN, TFPI2, CLDN5, UCHL1) known to be commonly aberrantly methylated in pancreatic ductal adenocarcinomas. The mean percentage of genes methylated in invasive ductal adenocarcinomas arising in association with an intraductal papillary mucinous neoplasm (mean +/- s.d., 81 +/- 17%) was significantly higher than that in noninvasive-intraductal papillary mucinous neoplasms (57 +/- 26%, P = 0.007) or peritumoral normal epithelial cells (22 +/- 17%, P < 0.0001). Carcinomas (intraductal papillary mucinous neoplasms with carcinoma in situ or their associated infiltrating adenocarcinoma) had significantly more methylated genes (71 +/- 19%) than low-grade (low and moderate dysplasia) intraductal papillary mucinous neoplasms (44 +/- 26%, P < 0.0001). The mean percentage of genes methylated in histologically normal pancreatic ductal cells from patients with ductal neoplasia (22 +/- 17%) was significantly higher than in normal ductal cells from patients with well-differentiated pancreatic endocrine neoplasms (4 +/- 7%, P = 0.002). Thus, aberrant DNA methylation increases with histologic grades of intraductal papillary mucinous neoplasm. Low-level aberrant methylation in the normal ductal cells is more prevalent in patients with ductal neoplasia than in controls without ductal neoplasms and may contribute to carcinogenesis. The detection of aberrant methylation in pancreatic cystic lesions could facilitate the diagnosis of intraductal papillary mucinous neoplasms.