Upregulation of epidermal growth factor receptor 4 in oral leukoplakia

Kobayashi, Hiroshi; Kumagai, Koshi; Gotoh, Akito; Eguchi, Takanori; Yamada, Hiroyuki; Hamada, Y.; Suzuki, Shigeharu; Suzuki, Ryuji

doi:10.1038/ijos.2013.10

Cited by 17 publications

(14 citation statements)

References 20 publications

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“…41,42 Further, high mRNA and protein expression of EGFR family members have been reported in so-called oral leukoplakia, an analogous clinicopathologic condition to esophageal epidermoid metaplasia, but in the oral cavity. 43,44 However, activating mutations in EGFR and HRAS comprise a minority of esophageal epidermoid metaplasia cases and, to date, have not been reported in esophageal squamous cell carcinoma. It should be reiterated that aberrant receptor tyrosine kinase/mitogen-activated protein kinase signal transduction may occur through multiple genetic and epigenetic mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Targeted next-generation sequencing supports epidermoid metaplasia of the esophagus as a precursor to esophageal squamous neoplasia

et al. 2017

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Esophageal epidermoid metaplasia is a rare condition that involves the proximal-to-middle third of the esophagus. It is sharply demarcated and defined histologically by epithelial hyperplasia, a prominent granular cell layer, and superficial hyperorthokeratosis. In addition, preliminary studies have suggested an association between esophageal epidermoid metaplasia and esophageal squamous neoplasia (squamous dysplasia and esophageal squamous cell carcinoma). To further characterize esophageal epidermoid metaplasia and better define its relationship to squamous neoplasia of the esophagus, we performed targeted next-generation sequencing on uninvolved esophageal squamous mucosa and matching esophageal epidermoid metaplasia specimens from 18 patients. Further, we evaluated both synchronous and metachronous high-grade squamous dysplasia/esophageal squamous cell carcinoma by next-generation sequencing from 5 of the 18 (28%) patients, and compared these findings to corresponding esophageal epidermoid metaplasia specimens. Targeted next-generation sequencing revealed 12 of 18 (67%) esophageal epidermoid metaplasia specimens' harbored alterations in genes often associated with esophageal squamous cell carcinoma. The most frequently mutated genes consisted of TP53 (n=10), PIK3CA (n=2), EGFR (n=2), MYCN (n=1), HRAS (n=1), and the TERT promoter (n=1). Sequencing of synchronous and metachronous high-grade squamous dysplasia/esophageal squamous cell carcinoma identified shared genetic alterations with corresponding esophageal epidermoid metaplasia specimens that suggests a clonal relationship between these entities. In addition, the presence of a TP53 mutation in esophageal epidermoid metaplasia specimens correlated with concurrent or progression to high-grade squamous dysplasia/esophageal squamous cell carcinoma. No genetic alterations were detected in uninvolved esophageal squamous mucosa. On the basis of these findings, we conclude esophageal epidermoid metaplasia is a precursor to in situ and invasive esophageal squamous neoplasia. Further, the detection of TP53 mutations in esophageal epidermoid metaplasia specimens may serve as an early detection biomarker for high-grade squamous dysplasia/esophageal squamous cell carcinoma.

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Section: Discussionmentioning

confidence: 99%

Targeted next-generation sequencing supports epidermoid metaplasia of the esophagus as a precursor to esophageal squamous neoplasia

et al. 2017

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“…While not looking at the PI3K pathway directly, Kobayashi et al compared the expression of EGFR‐like receptors and ligands in tissue samples between equal numbers of patients with lichen planus ( n = 10) and individuals without the disease. mRNA expression levels of EGFR mRNA were significantly higher among the OLP cohort.…”

Section: Could the Pi3k Pathway Play A Role In Facilitating Carcinogementioning

confidence: 99%

“…mRNA expression levels of EGFR mRNA were significantly higher among the OLP cohort. They suggested that the differential upregulation of both EGFR and its ligands might be sufficient to impact cell surface proto‐oncogenes and in that way provide a conduit of a path leading to OSCC .…”

Section: Could the Pi3k Pathway Play A Role In Facilitating Carcinogementioning

confidence: 99%

Could the PI3K canonical pathway be a common link between chronic inflammatory conditions and oral carcinogenesis?

Sonis

Mendes

2016

J Oral Pathology Medicine

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The association between chronic inflammatory disorders and oral carcinogenesis has been both a source of interest and contention. Based upon its central importance in oral carcinogenesis, the finding that the PI3k/Akt/mTOR pathway is activated in oral lichen planus, chronic graft-versus-host disease, and chronic oral candidiasis suggests that it may provide a link between benign and malignant oral conditions. Here, we discuss a possible mechanistic rationale that addresses the activation of this important signaling pathway and its downstream events, while correlating it with the carcinogenic potential of chronic oral disorders.

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“…EGFR family members include c-erbB1 (Her1), c-erbB2 (Her2-neu), c-erbB3 (Her3), and c-erbB4 (Her4). These subclasses have been studied in OED 20,23. Several reports demonstrate that c-erbB-2 expression increased progressively from non-dysplasia to dysplasia and OSCC 24–27.…”

Section: Introductionmentioning

confidence: 99%

Can Immunohistochemistry Serve as an Alternative to Subjective Histopathological Diagnosis of Oral Epithelial Dysplasia?

AbdulMajeed

Farah

2013

Biomark�Cancer

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Many attempts have been made to identify objective molecular biomarkers to diagnose and prognosticate oral epithelial dysplasia (OED) because histopathological interpretation is subjective and lacks sensitivity. The majority of these efforts describe changes in gene expression at protein level in OED as determined by immunohistochemistry (IHC). However, the literature on these putative markers of oral cancer progression is vast and varied. The main purpose of this article is to review current knowledge on biomarkers of protein expression for OED by IHC approaches. We further discuss these findings in terms of the proposed essential hallmarks of cancer cells to better understand their role in oral oncogenesis.

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Upregulation of epidermal growth factor receptor 4 in oral leukoplakia

Cited by 17 publications

References 20 publications

Targeted next-generation sequencing supports epidermoid metaplasia of the esophagus as a precursor to esophageal squamous neoplasia

Targeted next-generation sequencing supports epidermoid metaplasia of the esophagus as a precursor to esophageal squamous neoplasia

Could the PI3K canonical pathway be a common link between chronic inflammatory conditions and oral carcinogenesis?

Can Immunohistochemistry Serve as an Alternative to Subjective Histopathological Diagnosis of Oral Epithelial Dysplasia?

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