Overexpression of MDM2 protein in intrahepatic cholangiocarcinoma: relationship with p53 overexpression, Ki-67 labeling, and clinicopathological features.
Here we report the development of a genetically engineered mouse model of IHCC that incorporates two of the most common mutations in human IHCC, activating mutations of Kras (Kras(G12D)) and deletion of p53.
KRAS and p53 mutations are associated with an aggressive disease prognosis while FGFR mutations may signify a relatively indolent disease course of intrahepatic cholangiocarcinoma.
The systematic screening for p53 mutations in European patients with hilar cholangiocarcinoma has shown that the type of mutation (except 175) is different and its incidence is much lower when compared to the pattern previously reported for intrahepatic cholangiocarcinoma in East Asian patients.
Immunohistochemistry was performed on 6 mucinous and 12 conventional iCCs with matched age, sex, and stage, which revealed positive immunoreactivity in MUC1 (83% versus 58%), MUC2 (33% versus 17%), MUC5AC (100% versus 42%), MUC6 (50% versus 0), CK7 (83% versus 83%), CK20 (0 versus 17%), CDX2 (17% versus 0), p53 (67% versus 67%), Smad4 (67% versus 58%), and EGFR (83% versus 42%) in mucinous and conventional iCCs, respectively.
Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma.
We analyzed the loss of heterozygosity (LOH) and microsatellite instability (MSI) of hMSH2, hMLH1, and p53 genes in 55 patients with intrahepatic cholangiocarcinoma by using polymerase chain reaction based microsatellite markers D2S119, D3S1611, and TP53, respectively and determined the association between microsatellite alterations and patient survival.
This study examined the putative link between environmental carcinogens and intrahepatic cholangiocarcinoma by analysing DNA from 31 patients for complete p53 mutational signatures, using single strand conformational polymorphism and polymerase chain reaction.
The most common alterations were TP53, KRAS, and CDKN2A in gallbladder carcinoma; TP53, KRAS, PIK3CA, and BRAF in intrahepatic cholangiocarcinoma; and TP53 and SMAD4 in extrahepatic cholangiocarcinoma.
A tendency toward mutual exclusivity was seen between multiple genes in intrahepatic cholangiocarcinoma including <i>TP53:IDH1, IDH1:KRAS, TP53:BAP1</i>, and <i>IDH1:FGFR2</i> Alterations in CDKN2A/B and ERBB2 were associated with reduced survival and time to progression on chemotherapy in patients with locally advanced or metastatic disease.