review of literature on clinical pancreatology - The Pancreapedia

interventions. Cancer nests were manually miscrodissected from 8 LNM and 7 non-LNMpancreatic cancer tissues, and the protein extracts were then separated by difference gelelectrophoresis (DIGE) and identified by MALDI-TOF-TOF. Four differently regulatedproteins, ezrin, radixin, moesin, and c14orf166, were selected for further validation byWestern blot and immunohistochemistry. In DIGE analysis, it was identified 18 up-regulatedproteins and 15 down-regulated proteins in LNM pancreatic cancer nests compared withnon-LNM ones. Western blot and immunohistochemical analyses confirmed that radixin,moesin and c14orf166, but not ezrin, had significantly higher expression levels in LNMpancreatic cancers than in non-LNM controls. In conclusion, the specific protein pr<strong>of</strong>ilesfound in this study might provide new insights into the mechanism <strong>of</strong> lymph node metastasis.For the first time, c14orf166 was identified asa novel metastasis-associated protein, and theroles <strong>of</strong> radixin, moesin and c14orf166 in cancer metastasis deserve further investigations[406].Familial pancreatic cancerApproximately 5-10 percent <strong>of</strong> individuals with pancreatic cancer report a history <strong>of</strong>pancreatic cancer in a close family member. In addition, several known genetic syndromes,such as familial breast cancer (BRCA2), the Peutz-Jeghers syndrome, and the familialatypical multiple mole melanoma syndrome, have been shown to be associated with anincreased risk <strong>of</strong> pancreatic cancer. The known genes associated with these conditions canexplain only a portion <strong>of</strong> the clustering <strong>of</strong> pancreatic cancer in families, and research toidentify additional susceptibility genes is ongoing. Even in the absence <strong>of</strong> predictive genetictesting, the collection <strong>of</strong> a careful, detailed family history is an important step in themanagement <strong>of</strong> all patients with pancreatic cancer. While most pancreatic cancers that arisein patients with a family history are ductal adenocarcinomas, certain subtypes <strong>of</strong> pancreaticcancer have been associated with familial syndromes. Therefore, the histologic appearance<strong>of</strong> the pancreatic cancer itself, and/or the presence and appearance <strong>of</strong> precancerouschanges in the pancreas, may increase the clinical index <strong>of</strong> suspicion for a genetic syndrome[407].It has been reported that germline mutations in the palladin gene cause the familialaggregation <strong>of</strong> pancreatic cancer (in Seattle), but the evidence is weak and controversial. Itwas sequenced the coding regions <strong>of</strong> palladin gene in 48 individuals with familial pancreaticcancer. It was not found any deleterious mutations and find no evidence to implicatemutations in palladin gene as a cause <strong>of</strong> familial pancreatic cancer [408].Histologic precursorsPancreatic intraepithelial neoplasia (PanIN) is a precursor to invasive ductal adenocarcinoma<strong>of</strong> the pancreas. Observations made in genetically engineered mouse models suggest thatthe acinar/centroacinar compartment can give rise to ductal neoplasia. To integrate findingsin mice and men, it was examined human acinar cells, acinar-ductal metaplasia (ADM)lesions, and PanINs for KRAS2 gene mutations. Surgically resected pancreata werescreened for foci <strong>of</strong> ADM with or without an associated PanIN lesion. Stromal cells, acinarcells, ADMs, and PanINs were separately isolated using laser capture microdissection.KRAS2 status was analyzed using genomic DNA isolated from the microdissected tissue.Twelve <strong>of</strong> these 31 foci <strong>of</strong> ADM occurred in isolation, whereas 19 were in the same lobulesas a PanIN lesion. All 31 microdissected foci <strong>of</strong> acinar cells were KRAS2 gene wild-type, aswere all 12 isolated ADM lesions lacking an associated PanIN. KRAS2 gene mutations werepresent in 14 <strong>of</strong> 19 (74 %) PanIN lesions and in 12 <strong>of</strong> the 19 (63 %) foci <strong>of</strong> ADM associatedwith these PanINs. All ADM lesions with a KRAS2 gene mutation harbored the identical