NOTCH1 mutations as prognostic marker in oral squamous cell carcinoma.

Autor: Wu-Chou YH; Department of Medical Research and Development, Chang Gung Memorial Hospital at Linko, Taoyuan, Taiwan. Electronic address: yhwc8876@gmail.com., Hsieh CH; Department of Medical Oncology, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan, Taiwan., Liao CT; Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan, Taiwan., Lin YT; Department of Medical Research and Development, Chang Gung Memorial Hospital at Linko, Taoyuan, Taiwan., Fan WL; Genomic Medicine Core Laboratory, Department of Medical Research and Development, Chang Gung Memorial Hospital at Linko, Taoyuan, Taiwan., Yang CH; Department of Anatomic Pathology, Chang Gung Memorial Hospital at Keelung, Taiwan.
Jazyk: angličtina
Zdroj: Pathology, research and practice [Pathol Res Pract] 2021 Jul; Vol. 223, pp. 153474. Date of Electronic Publication: 2021 May 10.
DOI: 10.1016/j.prp.2021.153474
Abstrakt: Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity with poor prognosis. The dysregulation of Notch signaling pathway has been implicated in the OSCC tumorigenesis. However, the clinical implication of NOTCH1 mutation status in OSCC remains unelucidated. We extracted the NOTCH1 gene mutations from a whole exome sequencing dataset of 168 frozen OSCC tumor specimens and validated these NOTCH1 gene mutations by Sanger sequencing. We also assessed these NOTCH1 gene mutations and its pathological significance in our OSCC tumor tissues using immunohistochemistry. Univariate and multivariate analyses were also used to determine whether the association between NOTCH1 mutation status and prognostic factors was independent of other parameters. In this study, we have identified 44 (26.19 %) NOTCH1 gene mutations from a whole-exome sequencing of 168 OSCC formalin-fixed, paraffin-embedded (FFPE) tissue specimen. These mutations distributed in different NOTCH1 function domains, including the EGF-like repeats region, negative regulatory region, and Ankyrin repeats region. The immunohistochemical staining analysis revealed that NOTCH1 expression was increased in oral cancer tissues. In addition, of the 43 OSCC tumors with NOTCH1 mutations, we observed that the majority were negative for NOTCH1 intracellular domain 1 (NICD1) staining (76.74 %), and 10 tumors were positive for NICD1 staining (23.26 %). In conclusion, our study suggested that NOTCH1 expression is associated with the progression of OSCC. We also demonstrated that presence of a mutated NOTCH1 gene will help prognostic stratification in OSCC when combined with other clinicopathologic parameters.
(Copyright © 2021 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: