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Purpose: Hemostatic activation is common in pancreatic cancer and may be linked to angiogenesis and venous thromboembolism.We investigated expression of tissue factor (TF), the prime initiator of coagulation, in noninvasive and invasive pancreatic neoplasia.We correlatedTF expression with vascular endothelial growth factor (VEGF) expression, microvessel density, and venous thromboembolism in resected pancreatic cancer. Experimental Design: Tissue cores from a tri-institutional retrospective series of patients were used to build tissue microarrays. TF expression was graded semiquantitatively using immunohistochemistry in normal pancreas (n = 10), intraductal papillary mucinous neoplasms (n = 70), pancreatic intraepithelial neoplasia (n = 40), and resected or metastatic pancreatic adenocarcinomas (n = 130). Results: TF expression was observedin a majority of noninvasive and invasive pancreatic neoplasia, including 77% of pancreatic intraepithelial neoplasias, 91% of intraductal papillary mucinous neoplasms, and 89% of pancreatic cancers, but not innormalpancreas. Sixty-six of122 resectedpancreatic cancers (54%) were found to have high TF expression (defined as grade z2, the median score). Carcinomas with high TF expression were more likely to also expressVEGF (80% versus 27% with low TF expression, P < 0.0001) and had a higher median MVD (8 versus 5 per tissue core with low TF expression, P = 0.01). Pancreatic cancer patients with high TF expression had a venous thromboembolism rate of 26.3% compared with 4.5% in patients with low TF expression (P = 0.04). Conclusions: TF expression occurs early in pancreatic neoplastic transformation and is associated with VEGF expression, increased microvessel density, and possibly clinical venous thromboembolism in pancreatic cancer. Prospective studies evaluating the role of TF in pancreatic cancer outcomes are warranted.

Although still limited by sensitivity, molecular diagnostic strategies can detect the presence of neoplastic cells in the proximal airway of patients with surgically resectable NSCLC.

The p53 gene was sequenced in 100 primary human lung cancers by using direct dideoxynucleotide cycle sequencing and compared with sequence analysis by using the p53 GeneChip assay. Differences in sequence analysis between the two techniques were further evaluated to determine the accuracy and limitations of each method. p53 mutations were either detected by using both techniques or, if only detected by one technique, were confirmed by using mutation-specific oligonucleotide hybridization. Dideoxynucleotide sequencing of the conserved regions of the p53 gene (exons 5-9) detected 76% of the mutations within this region of the gene. The GeneChip p53 assay detected 81% of all (exons 2-11) mutations, including 80% of the mutations within the conserved regions of the gene. The GeneChip assay detected 46 of 52 missense mutations (88%), but 0 of 5 frameshift mutations. The specificity of direct sequencing and of the p53 GeneChip assay at detecting p53 mutations were 100% and 98%, respectively. The GeneChip p53 assay is a rapid and reasonably accurate approach for detecting p53 mutations; however, neither direct sequencing nor the p53 GeneChip are infallible at p53 mutation detection.