Wolf in sheep's clothing - Oral proliferative verrucous leukoplakia: Progression with longitudinal molecular insights.
Oral cavity keratinizing squamous cell carcinoma
Oral proliferative verrucous leukoplakia
TERT promoter mutations
p53
Journal
Annals of diagnostic pathology
ISSN: 1532-8198
Titre abrégé: Ann Diagn Pathol
Pays: United States
ID NLM: 9800503
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
received:
31
12
2022
accepted:
01
01
2023
pubmed:
15
1
2023
medline:
3
3
2023
entrez:
14
1
2023
Statut:
ppublish
Résumé
Oral proliferative verrucous leukoplakia (OPVL) is a chronic form of oral leukoplakia that progresses to a multifocal disease with confluent, exophytic and proliferative features. The clinical differential diagnosis for OPVL includes frictional keratosis, leukoplakia, chronic hyperplastic candidiasis, squamous papilloma, verrucous hyperplasia, verrucous carcinoma and squamous cell carcinoma. In this study, we aimed to delineate the dynamic changes in molecular signature during OPVL progression. We compare to a cohort of oral cavity keratinizing squamous cell carcinoma (OSCC) patients covering the spectrum of verrucous carcinoma to invasive squamous cell carcinoma including cytologically bland cuniculatum variant. Samples from a large OPVL lesion that exhibited a histopathologic continuum of OPVL progression. Canonical hotspot TERT promoter mutations were identified in all patients. TERT C228T was dominant and mutually exclusive with TERT C250T. In patients with TERT C250T, there was concurrent PI3 point mutation. TP53 mutations were also consistently found (8/10). At the protein level, p53 was abnormal, with loss of function and gain of function. OPVL is a pathology that shows proximity to the gene expression profile of OSCC, highlighting signatures in common that can be important targets for drug treatment, as well as in the development of diagnostic and prognostic strategies for this disease.
Sections du résumé
BACKGROUND
BACKGROUND
Oral proliferative verrucous leukoplakia (OPVL) is a chronic form of oral leukoplakia that progresses to a multifocal disease with confluent, exophytic and proliferative features. The clinical differential diagnosis for OPVL includes frictional keratosis, leukoplakia, chronic hyperplastic candidiasis, squamous papilloma, verrucous hyperplasia, verrucous carcinoma and squamous cell carcinoma. In this study, we aimed to delineate the dynamic changes in molecular signature during OPVL progression. We compare to a cohort of oral cavity keratinizing squamous cell carcinoma (OSCC) patients covering the spectrum of verrucous carcinoma to invasive squamous cell carcinoma including cytologically bland cuniculatum variant.
METHODS
METHODS
Samples from a large OPVL lesion that exhibited a histopathologic continuum of OPVL progression.
RESULTS
RESULTS
Canonical hotspot TERT promoter mutations were identified in all patients. TERT C228T was dominant and mutually exclusive with TERT C250T. In patients with TERT C250T, there was concurrent PI3 point mutation. TP53 mutations were also consistently found (8/10). At the protein level, p53 was abnormal, with loss of function and gain of function.
CONCLUSIONS
CONCLUSIONS
OPVL is a pathology that shows proximity to the gene expression profile of OSCC, highlighting signatures in common that can be important targets for drug treatment, as well as in the development of diagnostic and prognostic strategies for this disease.
Identifiants
pubmed: 36640643
pii: S1092-9134(23)00001-1
doi: 10.1016/j.anndiagpath.2023.152104
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
152104Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of competing interest We have no financial interest or conflict of interest in association with this work.