Interestingly, CLDN1 is expressed in recently described perineural-like

stromal proliferations in a small fraction of serrated colorectal polyps including MVHP and SSA/P [49]. These stromal pericryptal proliferations are usually focal and not exceeding 10% of polyp tissue; however, in rare cases, the spindle cells extensively populate the lamina propria to become a dominant cell population of the polyp. Previously reported colorectal lesions such as intestinal perineuriomas [50] and fibroblastic polyps [51] are most certainly exaggerated examples of these stromal proliferations and widen the spectrum of serrated colorectal polyps as the vast majority of these have the somatic BRAF V600E mutation [16]. This is the first report describing

a strong correlation between CLDN1 expression and BRAF V600E mutation status in serrated colorectal polyps. Akt inhibitor CLDN1 mRNA and protein expression was found to be significantly elevated in SSA/P and MVHP with BRAF V600E mutation. To date, there is no established direct link between the oncogenic and activating BRAF V600E mutation and regulation of CLDN1 expression. Our results support the view of a close relationship between BRAF mutated MVHP and SSA/P, which may, in fact, represent a continuous spectrum of the same neoplastic process Volasertib [27]. Precise subclassification of MVHP may require the use of additional ancillary techniques including CLDN1 immunohistochemistry to identify the lesions with different biologic potential for neoplastic progression to more advanced serrated pathway lesions. Supplementary figures. MC participated in study design, microarray analysis, performed RT-PCR and participated in data analysis and drafting manuscript. KYCF participated in data analysis and drafting of manuscript. JM participated in study design and Prostatic acid phosphatase patient selection, GVB participated in RT PCR, LJC contributed to study design

and drafting manuscript, MT contributed to patient selection and data analysis, GC performed mutational analysis of BRAF and KRAS, EB and LF participated in selection of polyp samples and immunohistochemistry scoring, TT and HT performed immunohistochemistry staining and DNA extraction. AR participated in study design, pathological examination of polyp samples and drafting of the manuscript. All authors read and approved manuscript. The authors thank Bill Wilson (CSIRO) for initial preliminary analysis of the microarray data. All authors declare no conflict of interest. “
“Pancreatic ductal adenocarcinoma (PC) is a highly malignant tumor that has a poor prognosis because of the lack of early symptoms. Familial pancreatic cancer (FPC) accounts for about 3% of all PC cases [1] and [2].