GNAS and KRAS Mutations are Common in Intraductal Papillary Neoplasms of the Bile Duct

GNAS and KRAS Mutations are Common in Intraductal Papillary Neoplasms of the Bile Duct

Intraductal papillary neoplasms of the bile duct (IPNB) shows favorable prognosis and is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Although activating point mutations of GNAS at codon 201 have been detected in approximately two thirds of IPM...

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Main Authors: Sasaki, Motoko, Matsubara, Takashi, Nitta, Takeo, Sato, Yasunori, Nakanuma, Yasuni
Format: Online
Language:English
Published: Public Library of Science 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847161/
id pubmed-3847161
recordtype oai_dc
spelling pubmed-38471612013-12-05 GNAS and KRAS Mutations are Common in Intraductal Papillary Neoplasms of the Bile Duct Sasaki, Motoko Matsubara, Takashi Nitta, Takeo Sato, Yasunori Nakanuma, Yasuni Research Article Intraductal papillary neoplasms of the bile duct (IPNB) shows favorable prognosis and is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Although activating point mutations of GNAS at codon 201 have been detected in approximately two thirds of IPMNs of the pancreas, there have been few studies on GNAS mutations in IPNBs. This study investigates the status of GNAS and KRAS mutations and their association with clinicopathological factors in IPNBs. We examined the status of GNAS mutation at codon 201 and KRAS mutation at codon 12&13, degree of mucin production and immunohistochemical expressions of MUC mucin core proteins in 29 patients (M/F = 15/14) with IPNB in intrahepatic and perihilar bile ducts (perihilar IPNB) and 6 patients (M/F = 5/1) with IPNB in distal bile ducts (distal IPNB). GNAS mutations and KRAS mutations were detected in 50% and 46.2% of IPNBs, respectively. There was no significant correlation between the status of GNAS mutation and clinicopathological factors in IPNBs, whereas, the status of KRAS mutation was significantly inversely correlated with the degree of MUC2 expression in IPNBs (p<0.05). All IPNBs with GNAS mutation only showed high-mucin production. Degree of mucin production was significantly higher in perihilar IPNBs than distal IPNBs (p<0.05). MUC2 and MUC5AC expression was significantly higher in IPNBs with high-mucin production than those with low-mucin production (p<0.01 and p<0.05, respectively). In conclusions, this study firstly disclosed frequent GNAS mutations in IPNBs, similarly to IPMNs. This may suggest a common histopathogenesis of IPNBs and IPMNs. The status of KRAS mutations was inversely correlated to MUC2 expression and this may suggest heterogeneous properties of IPNBs. IPNBs with high-mucin production are characterized by perihilar location and high expression of MUC2 and MUC5AC, irrespective of the status of GNAS and KRAS mutations. Public Library of Science 2013-12-02 /pmc/articles/PMC3847161/ /pubmed/24312577 http://dx.doi.org/10.1371/journal.pone.0081706 Text en © 2013 Sasaki et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Sasaki, Motoko
Matsubara, Takashi
Nitta, Takeo
Sato, Yasunori
Nakanuma, Yasuni
spellingShingle Sasaki, Motoko
Matsubara, Takashi
Nitta, Takeo
Sato, Yasunori
Nakanuma, Yasuni
GNAS and KRAS Mutations are Common in Intraductal Papillary Neoplasms of the Bile Duct
author_facet Sasaki, Motoko
Matsubara, Takashi
Nitta, Takeo
Sato, Yasunori
Nakanuma, Yasuni
author_sort Sasaki, Motoko
title GNAS and KRAS Mutations are Common in Intraductal Papillary Neoplasms of the Bile Duct
title_short GNAS and KRAS Mutations are Common in Intraductal Papillary Neoplasms of the Bile Duct
title_full GNAS and KRAS Mutations are Common in Intraductal Papillary Neoplasms of the Bile Duct
title_fullStr GNAS and KRAS Mutations are Common in Intraductal Papillary Neoplasms of the Bile Duct
title_full_unstemmed GNAS and KRAS Mutations are Common in Intraductal Papillary Neoplasms of the Bile Duct
title_sort gnas and kras mutations are common in intraductal papillary neoplasms of the bile duct
description Intraductal papillary neoplasms of the bile duct (IPNB) shows favorable prognosis and is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Although activating point mutations of GNAS at codon 201 have been detected in approximately two thirds of IPMNs of the pancreas, there have been few studies on GNAS mutations in IPNBs. This study investigates the status of GNAS and KRAS mutations and their association with clinicopathological factors in IPNBs. We examined the status of GNAS mutation at codon 201 and KRAS mutation at codon 12&13, degree of mucin production and immunohistochemical expressions of MUC mucin core proteins in 29 patients (M/F = 15/14) with IPNB in intrahepatic and perihilar bile ducts (perihilar IPNB) and 6 patients (M/F = 5/1) with IPNB in distal bile ducts (distal IPNB). GNAS mutations and KRAS mutations were detected in 50% and 46.2% of IPNBs, respectively. There was no significant correlation between the status of GNAS mutation and clinicopathological factors in IPNBs, whereas, the status of KRAS mutation was significantly inversely correlated with the degree of MUC2 expression in IPNBs (p<0.05). All IPNBs with GNAS mutation only showed high-mucin production. Degree of mucin production was significantly higher in perihilar IPNBs than distal IPNBs (p<0.05). MUC2 and MUC5AC expression was significantly higher in IPNBs with high-mucin production than those with low-mucin production (p<0.01 and p<0.05, respectively). In conclusions, this study firstly disclosed frequent GNAS mutations in IPNBs, similarly to IPMNs. This may suggest a common histopathogenesis of IPNBs and IPMNs. The status of KRAS mutations was inversely correlated to MUC2 expression and this may suggest heterogeneous properties of IPNBs. IPNBs with high-mucin production are characterized by perihilar location and high expression of MUC2 and MUC5AC, irrespective of the status of GNAS and KRAS mutations.
publisher Public Library of Science
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847161/
_version_ 1612032873312813056

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