Abstract
Background and AimsNext generation sequencing (NGS) has revealed a great deal about cancer-related somatic changes in esophageal squamous cell neoplasia; however, the changes in the very early stages remain unclear.ResultsTP53 (87%) and CDKN2A (20%) hot spot mutations were frequently found in early lesions. TP53 was the most common mutation (LGIN/HGIN, 86%; EP, 83%; LPM, 95%; MM/SM1, 80%), followed by CDKN2A (29%, 28%, 16% and 10%, respectively); the frequency of other mutations increased as the disease advanced (p < 0.01). Copy number variation analysis revealed copy number aberrations in multiple genes, including PIK3CA amplification (48%). NGS was superior to p53 immunostaining for detecting TP53 mutations (74% vs. 87%); in combination, the two tests improved detectability to 94%. Clinically, smoking was associated with the occurrence of TP53 mutations in these early lesions (p = 0.049).Materials and MethodsFifty-four early esophageal neoplasia lesions from 47 patients treated by endoscopic resection (low-grade intraepithelial neoplasia [LGIN], n = 1; high-grade intraepithelial neoplasia [HGIN] n = 7; invasion limited to epithelium [EP/M1], n = 18; lamina propria mucosae [LPM/M2], n = 19; muscularis mucosae [MM/M3], n = 8; and upper third of the SM [SM1], n = 2) were isolated from formalin-fixed paraffin-embedded tissue specimens by laser-capture microdissection. Target sequencing of 50 cancer-related genes was performed with an Ion Proton sequencer; their association with the clinical characteristics was investigated.ConclusionsMutations of TP53 and CDKN2A, and PIK3CA amplification were common in early esophageal squamous neoplasia, while other mutations accumulated with disease progression. An understanding of these molecular events might provide a molecular basis for early lesion treatment.
Highlights
Esophageal carcinoma is one of the most progressive types of cancer, and is the sixth and seventh leading cause of cancer-related mortality in the world and in Japan, respectively
Mutations of TP53 and CDKN2A, and PIK3CA amplification were common in early esophageal squamous neoplasia, while other mutations accumulated with disease progression
In Japan, early esophageal lesions are increasingly considered to be appropriate targets for endoscopic submucosal dissection (ESD)
Summary
Esophageal carcinoma is one of the most progressive types of cancer, and is the sixth and seventh leading cause of cancer-related mortality in the world and in Japan, respectively. The changes in early ESCC, and the genetic events occurring at the earliest stage of ESCC are not well understood In this background, the two most recent NGSbased studies from China reported the frequent presence of hotspot mutations as well as copy number aberrations in the early stages of ESCCs [3, 9]. The two most recent NGSbased studies from China reported the frequent presence of hotspot mutations as well as copy number aberrations in the early stages of ESCCs [3, 9] These observations were rather astonishing, since intraepithelial neoplasias (IENs) are generally considered to be premalignant, and treatment is not actively recommended [10]. Generation sequencing (NGS) has revealed a great deal about cancer-related somatic changes in esophageal squamous cell neoplasia; the changes in the very early stages remain unclear
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
