Distinctive clinicopathological features and KRAS and IDH 1/2 mutation status of cholangiolocellular carcinoma

2019 ◽  
Vol 50 (1) ◽  
pp. 84-91 ◽  
Author(s):  
Hironori Kusano ◽  
Yoshiki Naito ◽  
Yutaro Mihara ◽  
Reiichiro Kondo ◽  
Sachiko Ogasawara ◽  
...  
Keyword(s):  
Clinicopathological Features ◽  
Cholangiolocellular Carcinoma ◽  
Mutation Status

scholarly journals Intrahepatic cholangiocarcinomas with IDH1/2 mutation-associated hypermethylation at selective genes and their clinicopathological features

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kyoungbun Lee ◽  
Young Seok Song ◽  
Yoonju Shin ◽  
Xianyu Wen ◽  
Younghoon Kim ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cpg Island ◽  
Methylation Status ◽  
Intraepithelial Neoplasia ◽  
Clinicopathological Features ◽  
Isocitrate Dehydrogenase 1 ◽  
Cancer Specific Survival ◽  
Mutation Status ◽  
Mucin Production ◽  
Small Duct

Abstract Intrahepatic cholangiocarcinoma (ICC) is a rare but fatal tumor. The isocitrate dehydrogenase 1 and 2 (IDH1/2) genes are known to be mutated in ICC. IDH1/2 mutations tend to be accompanied by enhanced hypermethylation at a subset of genomic loci. We sought to clarify the clinicopathological features, including prognostic value, of ICCs with IDH1/2 mutation-associated hypermethylation at a subset of genes. The mutation status of IDH1/2 and methylation status of 30 gene CpG island loci were analyzed in 172 cases of ICC using pyrosequencing and the MethyLight assay, respectively. The mutation status of IDH1/2 was correlated with clinicopathological features and the DNA methylation status at 30 gene loci. Then, the clinicopathological characteristics were analyzed regarding three-tiered methylation statuses in genes showing IDH1/2 mutation-associated methylation. IDH1/2 mutations were found in 9.3% of ICCs, and IDH1/2-mutated tumors were associated with the histological subtype, including the bile ductular type and small duct type, and poor differentiation. Eight DNA methylation markers showed associations with IDH1/2 mutations, and ICCs with > 5/8 methylated markers were associated with the bile ductular type or small duct type, absence of mucin production, absence of biliary intraepithelial neoplasia, and presence of chronic liver disease. > 5/8 methylated markers were an independent prognostic marker associated with better survival in both cancer-specific survival and recurrence-free survival. In summary, by analyzing the association between IDH1/2 mutations and DNA methylation in individual genes, we developed a panel of DNA methylation markers that were significantly associated with IDH1/2 mutations and were able to identify a subset of ICC with better clinical outcomes.

scholarly journals Correlations Between the EGFR Mutation Status and Clinicopathological Features of Clinical Stage I Lung Adenocarcinoma

Medicine ◽  
2015 ◽  
Vol 94 (42) ◽  
pp. e1784 ◽  
Author(s):  
Tetsuya Isaka ◽  
Tomoyuki Yokose ◽  
Hiroyuki Ito ◽  
Masashi Nagata ◽  
Hideyuki Furumoto ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Clinical Stage ◽  
Clinicopathological Features ◽  
Stage I ◽  
Mutation Status

scholarly journals Expression of miRNAs in Papillary Thyroid Carcinomas Is Associated withBRAFMutation and Clinicopathological Features in Chinese Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Yun Sun ◽  
Shuang Yu ◽  
Yuanyuan Liu ◽  
Fen Wang ◽  
Yujie Liu ◽  
...  
Keyword(s):  
Cervical Lymph Node Metastasis ◽  
Clinicopathological Features ◽  
Tnm Stage ◽  
Chinese Patients ◽  
Papillary Thyroid ◽  
Mutation Status ◽  
Expression Levels ◽  
Thyroid Carcinomas ◽  
Enhanced Expression

MicroRNAs (miRNAs) dysregulation has been shown to play a critical regulatory role in papillary thyroid carcinomas (PTCs).BRAFmutation is associated with poor clinicopathological outcomes in PTC. In order to identify a possible association between dysregulated miRNA expression andBRAFmutation as well as clinicopathological features in Chinese patients with PTC, we examined the expression levels of five reported dysregulated miRNAs (miRNA-221, miRNA-222, miRNA-146b, miRNA-181, and miRNA-21) and determinedBRAFmutation status in 52 patients with PTC and 52 patients with benign thyroid nodules (BTNs). The expression levels of all five miRNAs were significantly increased in PTC when compared to BTN. TheBRAFmutation occurred more frequently in PTC cases with advanced TNM stage. Importantly, miRNA-221, miRNA-222, miRNA-146b, and miRNA-181 expression levels were significantly higher in PTC patients withBRAFmutation. In addition, enhanced expression of miRNA-221 and miRNA-222 was found in patients with cervical lymph node metastasis and advanced TNM stage. Increased expression of miRNA-221 and miR-181 was evidenced in patients with larger tumors. These findings showed a potential role of this distinct profile of miRNAs in differentiating PTC from BTN.BRAFmutation might regulate or interact with miRNA in the pathogenesis and progression of PTC.

scholarly journals GATA3 somatic mutations are associated with clinicopathological features and expression profile in TCGA breast cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fahimeh Afzaljavan ◽  
Ayeh Sadat Sadr ◽  
Sevtap Savas ◽  
Alireza Pasdar
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Overall Survival ◽  
Somatic Mutations ◽  
Cox Regression ◽  
Expression Profiles ◽  
Clinicopathological Features ◽  
Breast Cancer Patients ◽  
Mutation Status ◽  
Er Positive

AbstractThe effect of somatic mutations and the gene expression profiles on the prognosis is well documented in cancer research. This study was conducted to evaluate the association of GATA3 somatic mutations with tumor features, survival, and expression profiles in breast cancer. Clinicopathological information was compared between TCGA-BRCA patients with GATA3-mutant and non-mutant tumors in all patients as well as in ER-positive subgroup. Cox-regression method was used to evaluate the association of the GATA3 mutation status with overall survival time. Differential gene expression, functional annotation, and protein–protein interaction analyses were performed using edgeR, Metascape, DAVID, STRING and CytoNCA. GATA3-mutant and non-mutant samples had significantly different clinicopathological features (p < 0.05). While GATA3 mutation status was not associated with the overall survival in the entire cohort (padj = 0.52), the GATA3-wild type ER-positive cases had a better prognosis than mutant ones (padj = 0.04). GATA3 expression was higher in tumors than normal tissues. Several pathways were different between mutant and non-mutant groups (p < 0.05). Interleukin-6 was found as the highest scored gene in both comparisons (normal vs. mutant and normal vs. non-mutant groups) in the entire patient and in the ER-positive subgroup, suggesting the association of IL6 with breast tumorigenesis. These findings suggest that GATA3 mutations can be associated with several tumor characteristics and influence the pattern of gene expression. However, GATA3 mutation status seems to be a prognostic factor for the disease only in ER-positive patients.

Expression analysis of MET, EGFR, and HER2, and K-ras mutation status in patients with stage II/III gastric cancer enrolled in the ACTS-GC study.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 40-40
Author(s):  
Atsushi Ochiai ◽  
Koji Kitada ◽  
Wataru Ichikawa ◽  
Masanori Terashima ◽  
Issei Kurahashi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinicopathological Features ◽  
Stage Ii ◽  
Intestinal Type ◽  
Her2 Overexpression ◽  
Diffuse Type ◽  
Ras Mutation ◽  
Mutation Status ◽  
Expression Levels ◽  
Met Amplification

40 Background: Exploratory biomarker analysis was conducted to identify factors related to outcomes of patients enrolled in the ACTS-GC study, a randomized controlled trial comparing surgery followed by adjuvant S-1 therapy with surgery alone in 1,059 patients with stage II/III gastric cancer. Methods: Formalin-fixed paraffin-embedded specimens obtained from 105 patients, an institutional subset of this biomarker study of 829 patients, were extensively examined for EGFR and HER2 by immunohistochemistry (IHC), MET amplification by FISH, and K-ras mutation status (codon 12, 13) by PNA-enriched direct sequencing. The expressions of 63 genes involved in pyrimidine metabolic pathway, growth factor signaling pathway, apoptosis, DNA repair, etc., were measured by quantitative real-time RT-PCR. The relations of the expressions of these genes to clinicopathological features such as histological type, T grade, N grade, tumor stage, gender, and age were also investigated. Results: The rates of K-ras mutation, EGFR overexpression, HER2 overexpression, and MET amplification were 6.7% (7/105), 14.3% (15/105), 11.4% (12/105), and 21.0% (22/105), respectively. These factors were almost mutually exclusive. Co-expressions were seen in 2 (EGFR & HER2), 4 (HER2 & MET), 5 (MET and EGFR) and 1 (EGFR & HER2 & MET) of the 105 patients. MET amplification and EGFR overexpression were associated with worse outcomes. In contrast, KRAS and HER2 status were not associated with overall survival or relapse-free survival. Expression levels of PCAM1, ESR1, MUC2, CAV1, ITGB3, and APC mRNA were significantly higher in diffuse-type cancer than in intestinal-type cancer, whereas expression levels of HER2, E2F1, LDHA and TOP2A mRNA were significantly higher in intestinal-type than in diffuse-type cancer (FDR P<0.05). Associations of other clinically significant genes with clinicopathological features other than histologic type were not screened. Conclusions: Many clinical, pathological, molecular, and genetic factors have been investigated with a growing understanding of the molecular pathogenesis of gastric cancer. We review and discuss such prognostic markers in the ACTS-GC study.

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