Chromogenic In Situ Hybridization Analysis of Epidermal Growth Factor Receptor Gene/Chromosome 7 Numerical Aberrations in Hepatocellular Carcinoma Based on Tissue Microarrays

Tsiambas, Evangelos; Manaios, Loukas; Papanikolopoulos, Costas; Rigopoulos, Dimitrios; Tsounis, Dimitrios; Karameris, Andreas; Soultati, Aspasia; Koliopoulou, Antigone; Kravvaritis, Christos; Sergentanis, Theodoros N.; Patsouris, Efstratios; Dourakis, Spyridon P.

doi:10.1007/s12253-008-9146-5

Cited by 9 publications

(6 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our autopsy cohort, EGFR overexpression was found to be related to more differentiated HCC. Previous studies have presented conflicting results on this topic, either reporting detection of higher EGFR expression in high-grade tumors [18,19] or demonstrating a complete absence of any association [20,21] . Our findings are similar to those described by Morimitsu et al [22] , who showed a progressive loss of EGFR expression in less differentiated HCC in surgical specimens.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemistry panel segregates molecular types of hepatocellular carcinoma in Brazilian autopsy cases

Felipe-Silva¹,

Wakamatsu²,

Cirqueira³

et al. 2016

WJG

View full text Add to dashboard Cite

AIM:To assess the distribution of proteins coded by genes reported as relevant for the molecular classification of hepatocellular carcinoma (HCC). METHODS:In this retrospective cross-sectional study, the following clinicopathological data were analyzed in 80 autopsied HCC patients: sex, age, ethnicity, alcohol intake, infection with hepatitis B and/or C virus, infection with human immunodeficiency virus, prior treatment, basic and immediate causes of death, liver weight, presence of cirrhosis, number and size of nodules, gross pattern, histological grade and variants, architectural pattern, invasion of large veins, and presence and location of extrahepatic metastases. The protein products of genes known to be involved in molecular pathogenesis of HCC, including epidermal growth factor receptor (EGFR), MET, keratin 19 (K19), vimentin, beta-catenin, mechanistic target of rapamycin (mTOR), extracellular signaling-related RESULTS:Infection with hepatitis C virus was identified in 49% of the 80 autopsy patients, cirrhosis in 90%, advanced tumors in 95%, and extrahepatic metastases in 38%. Expression of K19, p53 and ERK1 correlated to high-grade lesions. Expression of ERK1, nuclear beta-catenin, cyclin D1 and ERK2 correlated to higher rates of cell proliferation as determined by Ki67. Expression of MET, EGFR (> 0) and caspase 3 correlated with lower histological grades. Expression of EGFR correlated to that of caspase 3, and overexpression of EGFR (≥ 200/300) was observed in low-grade tumors more frequently (grades 1 and 2: 67% vs grade 3: 27% and grade 4: 30%). Expression of ERK1 was associated with that of K19 and vimentin, whereas expression of ERK2 was associated with that of cyclin D1, MET and membrane beta-catenin. Expression of vimentin was strongly correlated with that of K19. CONCLUSION:Expression of K19, p53, ERK1, ERK2, vimentin and nuclear beta-catenin was related to highergrade markers, as opposed to expression/overexpression of EGFR, MET and caspase 3.

show abstract

Section: Discussionmentioning

confidence: 99%

Immunohistochemistry panel segregates molecular types of hepatocellular carcinoma in Brazilian autopsy cases

Felipe-Silva¹,

Wakamatsu²,

Cirqueira³

et al. 2016

WJG

View full text Add to dashboard Cite

show abstract

“…EGFR overexpression is detected in many epithelial cancers including lung cancer, colorectal cancer, head and neck cancer, and HCC [ 10 – 17 ]. EGFR overexpression has been observed in 29–85% of HCC tissues [ 13 – 17 ]. In this study, EGFR overexpression was detected in both HCC (32.5%) and matched nontumor tissues (28.6%).…”

Section: Discussionmentioning

confidence: 99%

“…Ligand binding to the extracellular domain of EGFR results in receptor dimerization, transphosphorylation of the tyrosine residues in cytoplasmic domain, and activation of downstream signaling [ 9 ]. EGFR is highly expressed in many epithelial cancers, including lung cancer, colorectal cancer, head and neck cancer, and HCC [ 10 – 17 ]. EGFR overexpression is observed in 29–85% of HCC tissues [ 13 – 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…EGFR is highly expressed in many epithelial cancers, including lung cancer, colorectal cancer, head and neck cancer, and HCC [ 10 – 17 ]. EGFR overexpression is observed in 29–85% of HCC tissues [ 13 – 17 ]. The high percentage of EGFR overexpression in HCC has led to the suggestion of EGFR as a therapeutic target for the treatment of HCC [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Missense Mutations in Exons 18–24 of EGFR in Hepatocellular Carcinoma Tissues

Panvichian

Tantiwetrueangdet

Sornmayura

et al. 2015

BioMed Research International

View full text Add to dashboard Cite

Epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase receptor, plays important roles in various cancers. In nonsmall cell lung cancer (NSCLC), EGFR mutations cluster around the ATP-binding pocket (exons 18–21) and some of these mutations activate the kinase and induce an increased sensitivity to EGFR-tyrosine kinase inhibitors. Nevertheless, data of EGFR mutations in HCC are limited. In this study, we investigated EGFR expression by immunohistochemistry and EGFR mutations (exons 18–24) by PCR cloning and sequencing. EGFR overexpression in HCC and matched nontumor tissues were detected in 13/40 (32.5%) and 10/35 (28.6%), respectively. Moreover, missense and silent mutations were detected in 13/33 (39.4%) and 11/33 (33.3%) of HCC tissues, respectively. The thirteen different missense mutations were p.L730P, p.V742I, p.K757E, p.I780T, p.N808S, p.R831C, p.V851A, p.V897A, p.S912P, p.P937L, p.T940A, p.M947V, and p.M947T. We also found already known SNP, p.Q787Q (CAG>CAA), in 13/33 (39.4%) of HCC tissues. However, no significant association was detected between EGFR mutations and EGFR overexpression, tissue, age, sex, tumor size, AFP, HBsAg, TP53, and Ki-67. Further investigation is warranted to validate the frequency and activity of these missense mutations, as well as their roles in HCC tumorigenesis and in EGFR-targeted therapy.

show abstract

“…For example, the mutations of the target genes may be involved in the sensitivity to the molecularly targeted therapies for HCC, because somatic mutations in the exons 18-21 of EGFR that are strongly correlated with robust clinical response to gefitinib treatment in patients with non-small cell lung cancer [186,187]. In HCC, however, there are controversial studies reporting no mutations [188,189], a missense mutation [190], or numerical alteration [191] in the EGFR gene and the correlation of these changes with the sensitivity to the molecularly targeted therapies is as yet unclear. In contrast, baseline circulating endothelial progenitor cell level is reported to be a predictor of the efficacy of sorafenib plus metronomic oral tegafur/ uracil [192], as are the plasma levels of angiopoietin-2, VEGFR-2, and EGFR for the combination therapy of bevacizumab and erlotinib [111].…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Evolving Molecular Mechanism-Based Strategies for Control of Hepatocellular Carcinoma

Sato¹,

Mori

2011

CMC

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide. Unresectable or metastatic HCC has a poor prognosis, and systemic cytotoxic chemotherapy has failed to show a substantial benefit for patients with HCC. However, there has been increasing interest in developing novel molecularly targeted agents in HCC due to the accumulation of knowledge of cell signaling and molecular carcinogenesis. Furthermore, some of these agents have proven to be efficacious in other traditionally challenging carcinomas, such as renal cell carcinoma. Recently, a phase III, randomized, placebo-controlled trial demonstrated that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor and Ras kinase, improves overall survival (OS) in patients with advanced HCC. This seminal study described the first agent to improve OS in HCC and began a new era of molecule-targeted cancer therapies. Currently, many novel molecularly targeted agents are under evaluation in clinical trials. In this review, we comprehensively summarize the molecular pathogenesis, targets, and signal transduction pathways involved in HCC. We also detail the current status of molecularly targeted agents that are under clinical development in advanced HCC, including the mechanisms of action of these agents.

show abstract

Chromogenic In Situ Hybridization Analysis of Epidermal Growth Factor Receptor Gene/Chromosome 7 Numerical Aberrations in Hepatocellular Carcinoma Based on Tissue Microarrays

Cited by 9 publications

References 42 publications

Immunohistochemistry panel segregates molecular types of hepatocellular carcinoma in Brazilian autopsy cases

Immunohistochemistry panel segregates molecular types of hepatocellular carcinoma in Brazilian autopsy cases

Missense Mutations in Exons 18–24 of EGFR in Hepatocellular Carcinoma Tissues

Evolving Molecular Mechanism-Based Strategies for Control of Hepatocellular Carcinoma

Contact Info

Product

Resources

About