The First Part Of The Prognostic Significance Of DAXX Gene Mutation In Pancreatic Neuroendocrine Tumors The Second Part Of Pancreatic Neuroendocrine Tumors In The Expression Of MAP2, MAP1B And Its Prognostic Significance

Backgroud and aims:The death domain-associated protein 6(DAXX)is a protein that is encoded by the DAXX gene,which can induce apoptosis through the Fas receptor or JNK pathway.In recent years,studies have found that more than 25%of PNETs patients had DAXXgerne mutation,and DAXX gene mutation associated with prognosis.However,wheather the prognosis of patients with DAXX gene mutation is controversial.At the same time,more than 90%of the PNETs patients included in the present study were nonfunctional pancreatic neuroendocrine tumors,and the functional PNETs were very few.Therefore,our aim is to study whether DAXX gene mutation is different in subgroup of PNETs and to explore the relationship between DAXX gene mutation and prognosis of PNETs patients.Methods:PCR amplification of the exons of DAXX gene,followed by Sanger sequencing detection of the exon gene sequence,and then analyzed the gene mutation sites and mutation types.We statistically analyzed the DAXX gene mutation in the subgroup of PNETs(ie,insulin and non-insulinoma,functional PNETs and non-functional PNETs),and correlated DAXX gene mutation with the clinicopathological features and prognosis in PNETs patients.Results:23.0%(26/113)of PNETs patients had DAXX gene mutation.There were no significant differences in DAXX gene mutations between the subgroup of PNETs(p>0.05).77%of the gene mutation sites are located in the HAUSP interacting domain of the DAXX protein.DAXX gene mutations were associated with large tumors(3.8 cm vs.2.5 cm,p = 0.035),poor overall survival(Log Rank p = 0.008)and poor disease-free survival(Log rank p = 0.003)in patients with PNETs,but DAXX gene mutation is not independent predictor for PNETs patients.Conclusion:There were no significant differences in subtype of PNETs in DAXX gene mutation.PNETs paients with DAXX gene mutation had poor survival than those without DAXX gene mutation.Purpose:To determine whether microtubule-associated protein 2(MAP2)and microtubule-associated protein 1B(MAP1 B)could be prognostic biomarkers for patients with pancreatic neuroendocrine tumors(PNETs).Methods:With immunohistochemical staining,the expression of MAP2 and MAP1B was examined in 193 and 120 primary tumors,respectively.The expression of each protein was correlated with clinicopathological characteristics including prognosis.Results:MAP2 and MAP1B were expressed in 88 of 193(45.6%)and 77 of 120(64.2%)tumors,respectively.Expression of MAP2 was significantly associated with favorable overall survival in patients with PNETs(Log rank p=0.012),as well as in patients with noninsulinomas and NF(Log rank p are 0.029).Moreover,MAP2 expression was associated with better overall survival in a subset of patients with tumors at stage ? and stage ?(Log rank p=0.017).MAP1B expression did not correlate with prognosis.Conclusion:MAP 2 could be a novel,independent prognostic biomarker for PNETs.