Targeted next-generation sequencing supports epidermoid metaplasia of the esophagus as a precursor to esophageal squamous neoplasia
| العنوان: | Targeted next-generation sequencing supports epidermoid metaplasia of the esophagus as a precursor to esophageal squamous neoplasia |
|---|---|
| المؤلفون: | Marcia I. Canto, Dora Lam-Himlin, Elizabeth A. Montgomery, Aatur D. Singhi, Lysandra Voltaggio, Marina N. Nikiforova, Kevin McGrath, Christina A. Arnold |
| المصدر: | Modern Pathology. 30:1613-1621 |
| بيانات النشر: | Elsevier BV, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Pathology, Esophageal Neoplasms, Biology, Esophageal Diseases, Pathology and Forensic Medicine, Surgical pathology, 03 medical and health sciences, Esophagus, 0302 clinical medicine, Carcinoma, medicine, Humans, HRAS, neoplasms, Aged, Aged, 80 and over, Metaplasia, High-Throughput Nucleotide Sequencing, Anatomical pathology, Middle Aged, medicine.disease, stomatognathic diseases, 030104 developmental biology, medicine.anatomical_structure, Cytopathology, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Immunohistochemistry, Female, Esophageal Squamous Cell Carcinoma, Hematopathology, Precancerous Conditions |
| الوصف: | 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. |
| تدمد: | 0893-3952 |
| DOI: | 10.1038/modpathol.2017.73 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e6cf3a2743041b71f5b1c6cba3ce98cc https://doi.org/10.1038/modpathol.2017.73 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e6cf3a2743041b71f5b1c6cba3ce98cc |
| قاعدة البيانات: | OpenAIRE |
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