Gene amplification and protein overexpression of HER-2/neu in human extrahepatic cholangiocarcinoma as detected by chromogenic in situ hybridization and immunohistochemistry: its prognostic implication in node-positive patients

Kim, H.J.; Yoo, Taeyong; Park, D.I.; Park, J.H.; Cho, Y.K.; Sohn, Chong Il; Jeon, Woo Kyu; Kim, B.I.; Kim, M.K.; Chae, Seung Wan; Sohn, Jin Hee

doi:10.1093/annonc/mdm006

Cited by 47 publications

(31 citation statements)

References 21 publications

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“…Before the implementation of next-generation sequencing technologies, our knowledge of the role of mutations in iCCA was limited, encompassing recurrent activating mutations in KRAS (19%), low frequency mutations in BRAF (5%), and EGFR (3%), and widely varying reports of loss-offunction mutations in the tumor suppressor TP53 (16%, range 1%-38%; Tables 1 and 2; refs. 31,[50][51][52][53][54][55][56][57][58][59][60][61][62][63][64]. While KRAS and TP53 mutations are relatively common in all CCA, mutations in IDH1/2 and BRAF are considerably more prevalent in iCCA (Table 1).…”

Section: Molecular Pathogenesismentioning

confidence: 99%

Molecular Pathogenesis and Targeted Therapies for Intrahepatic Cholangiocarcinoma

Moeini

Sia

Bardeesy

et al. 2016

Clinical Cancer Research

205

176

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Intrahepatic cholangiocarcinoma (iCCA) is a molecularly heterogeneous hepatobiliary neoplasm with poor prognosis and limited therapeutic options. The incidence of this neoplasm is growing globally. One third of iCCA tumors are amenable to surgical resection, but most cases are diagnosed at advanced stages with chemotherapy as the only established standard of practice. No molecular therapies are currently available for the treatment of this neoplasm. The poor understanding of the biology of iCCA and the lack of known oncogenic addiction loops has hindered the development of effective targeted therapies. Studies with sophisticated animal models defined IDH mutation as the first gatekeeper in the carcinogenic process and led to the discovery of striking alternative cellular origins. RNA-and exome-sequencing technologies revealed the presence of recurrent novel fusion events (FGFR2 and ROS1 fusions) and somatic mutations in metabolic (IDH1/2) and chromatinremodeling genes (ARID1A, BAP1). These latest advancements along with known mutations in KRAS/BRAF/EGFR and 11q13 high-level amplification have contributed to a better understanding of the landscape of molecular alterations in iCCA. More than 100 clinical trials testing molecular therapies alone or in combination with chemotherapy including iCCA patients have not reported conclusive clinical benefits. Recent discoveries have shown that up to 70% of iCCA patients harbor potential actionable alterations that are amenable to therapeutic targeting in early clinical trials. Thus, the first biomarkerdriven trials are currently underway.

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Section: Molecular Pathogenesismentioning

confidence: 99%

Molecular Pathogenesis and Targeted Therapies for Intrahepatic Cholangiocarcinoma

Moeini

Sia

Bardeesy

et al. 2016

Clinical Cancer Research

205

176

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“…Its amplification or overexpression has been shown to play an important role in the development and progression of several solid tumor malignancies, and is an effective therapeutic target in breast and gastric cancer (41)(42)(43). Studies evaluating HER-2 overexpression in BC have identified HER-2 mutations in gallbladder (about 10%) and EHCCs (up to 25%), and have been associated with a more aggressive phenotype (27,44). While small case series demonstrated anti-tumor activity with anti HER-2 directed therapy in patients whose tumors expressed HER-2 overexpression or amplification, these findings did not translate in BC patients Novel genomic alterations identified in IHCC…”

Section: Her-2/neu Genementioning

confidence: 99%

Biliary cancer: intrahepatic cholangiocarcinoma vs. extrahepatic cholangiocarcinoma vs. gallbladder cancers: classification and therapeutic implications

Ahn

Bekaii‐Saab

2017

J. Gastrointest. Oncol.

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Biliary cancers (BCs) are a diverse group of tumors that arise from the bile duct epithelium and are divided into cholangiocarcinomas of the intrahepatic and extrahepatic cholangiocarcinoma (EHCC) and cancer of the gallbladder. Despite improvements in treatment and diagnosis, BCs are often diagnosed at an advanced stage and associated with poor prognosis and limited treatment options. Recent discoveries have allowed us to have a better understanding of the genomic diversity in BC, and identify genes that are likely contributing to its pathogenesis, proliferation and treatment resistance. Additionally, these advances have allowed us to reason that each anatomic group within BC behave as distinct diseases, with differences in prognosis and outcomes. Based on this knowledge, recent advances have allowed us to identify actionable mutations that form rational therapeutic targets with novel agents, where their relevance will be better understood through the completion of prospective clinical trials.

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“…In CC, however, four groups have examined HER-2/neu expression using IHC and found no correlation with survival (61,62,74,75).…”

Section: Epidermal Growth Factor Receptor (Egfr) Familymentioning

confidence: 99%

Prognostic molecular markers in cholangiocarcinoma: A systematic review

Briggs

Neal

Mann

et al. 2009

European Journal of Cancer

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The worldwide incidence of cholangiocarcinoma (CC) is steadily rising, the United Kingdom incidence now exceeding 1000 cases per year. It is an aggresive malignancy typified by unresponsiveness to existing chemotherapy and radiotherapy regimes in the vast majority of cases. Surgery offers the only hope of a cure, though postoperative disease recurrence is common, with 5-year survival rates following resection of less then 25%. Developments in molecular techniques and improved understanding of the basis of carcinogenesis in CC has led to examination of the role of biomarkers in predicting poor outcome. This systematic review examines published evidence relating to the prognostic significance of these molecular markers in CC. Of the molecular markers which have been investigated to date p53 mutation, cyclins, proliferation indices, mucins, CA19-9, CRP, and aneuploidy appear to hold significant potential as predictors of outcome in CC. These and other biomarkers may themselves represent novel therapeutic targets for CC.

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Gene amplification and protein overexpression of HER-2/neu in human extrahepatic cholangiocarcinoma as detected by chromogenic in situ hybridization and immunohistochemistry: its prognostic implication in node-positive patients

Cited by 47 publications

References 21 publications

Molecular Pathogenesis and Targeted Therapies for Intrahepatic Cholangiocarcinoma

Molecular Pathogenesis and Targeted Therapies for Intrahepatic Cholangiocarcinoma

Biliary cancer: intrahepatic cholangiocarcinoma vs. extrahepatic cholangiocarcinoma vs. gallbladder cancers: classification and therapeutic implications

Prognostic molecular markers in cholangiocarcinoma: A systematic review

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