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.
Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma.
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.
In conclusion, MDM2 amplification in large-duct iCCAs is more common than presently considered, and it may represent a unique biliary carcinogenetic process in which KRAS and TP53 mutations are less frequent.
The most frequent genetic aberrations (GAs) observed were tumor protein 53 (TP53; 27%), cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B; 27%), KRAS (22%), AT-rich interactive domain-containing protein 1A (ARID1A; 18%), and isocitrate dehydrogenase 1 (IDH1; 16%) in IHCCA; KRAS (42%), TP53 (40%), CDKN2A/B (17%), and SMAD4 (21%) in EHCCA; and TP53 (59%), CDKN2A/B (19%), ARID1A (13%), and ERBB2 (16%) in GBCA.
The presence of mutations in ARID1A, PIK3C2G, STK11, TGFBR2, and TP53 genes was significantly associated with poor prognosis in patients with ICC (p = 0.012, p = 0.030, p = 0.030, p = 0.011, and p = 0.011, respectively).
KRAS and p53 mutations are associated with an aggressive disease prognosis while FGFR mutations may signify a relatively indolent disease course of intrahepatic cholangiocarcinoma.
To investigate whether IDH1R132C mutant in combination with loss of p53 and activated Notch signaling promotes intrahepatic cholangiocarcinoma (ICC) development.
IDH1/2 (p=0.0005) and BAP1 (p=0.0097) mutations were characteristic of ICC, while KRAS (p=0.0019) and TP53 (p=0.0019) were more frequent in ECC and GBC.
We performed a case-control association study to evaluate the association between common polymorphisms in MTHFR (C677T and A1298C) and the Arg72Pro polymorphism in the p53 gene and the risk for cervical intraepithelial neoplasia (CIN) or invasive cervical cancer (ICC) in Mexican HPV-infected women.
We find that TP53-defective ICC patients are more likely to be HBsAg-seropositive, whereas mutations in the oncogene KRAS are nearly exclusively found in HBsAg-seronegative ICC patients.
IDH1 and IDH2 mutations were significantly associated with increased levels of p53 in intrahepatic cholangiocarcinomas, but no mutations in the p53 gene were found, suggesting that mutations in IDH1 and IDH2 may cause a stress that leads to p53 activation.
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.
Intrahepatic cholangiocarcinoma (CCA) is a lethal malignancy of the biliary epithelium associated with p53 mutations, bile duct injury, inflammation, and fibrosis.
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.
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.
Overexpression of MDM2 protein in intrahepatic cholangiocarcinoma: relationship with p53 overexpression, Ki-67 labeling, and clinicopathological features.
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.
In conclusion, we show that 1 putative tumor-suppressor gene on 8p22 may relate to progression of ICC and suggest that the p53 tumor-suppressor gene may be associated with carcinogenesis of ICC.