The Diagnostic Utility of RAS Q61R Mutation-specific Immunohistochemistry in Epithelial-Myoepithelial Carcinoma.
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ genetics
DNA Mutational Analysis
Diagnosis, Differential
Female
Humans
Immunohistochemistry
Japan
Male
Middle Aged
Mutation
Myoepithelioma
/ genetics
Neoplasms, Glandular and Epithelial
/ genetics
Predictive Value of Tests
Proto-Oncogene Proteins p21(ras)
/ genetics
Reproducibility of Results
Retrospective Studies
Salivary Gland Neoplasms
/ genetics
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
01 07 2021
01 07 2021
Historique:
pubmed:
23
1
2021
medline:
14
9
2021
entrez:
22
1
2021
Statut:
ppublish
Résumé
Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland cancer characterized by biphasic tubular structures composed of inner ductal and outer clear myoepithelial cells. Because of its histologic variety and overlap of histologic features with other salivary gland tumors, there are broad differential diagnoses. The HRAS Q61R mutation has been reported to be frequent in and specific to EMC. We evaluated the usefulness of RAS Q61R mutant-specific immunohistochemical (IHC) staining for detecting this genetic alteration in EMC. We investigated 83 EMC cases and 66 cases of salivary gland tumors with an EMC-like component, including pleomorphic adenoma, adenoid cystic carcinoma, basal cell adenoma/adenocarcinoma, and myoepithelial carcinoma. Sanger sequencing was performed for HRAS, KRAS, and NRAS. The diffuse and membranous/cytoplasmic RAS Q61R IHC expression was observed in 65% of EMC cases, in which all cases harbored the HRAS Q61R mutation. IHC-positive cases were present only in de novo EMCs (54/76 cases, 71%) but not in EMCs ex pleomorphic adenoma. The immunoreactivity was almost always restricted to the myoepithelial cells. Conversely, all EMC cases lacking the HRAS Q61R mutation were negative on IHC. In addition, only 3% of EMC-like tumors showed the abovementioned immunopositivity. None of the cases examined carried KRAS or NRAS mutations. IHC for RAS Q61R is highly sensitive and specific for detecting the HRAS Q61R mutation in EMC. Since significant immunopositivity was almost exclusively identified in nearly two thirds of EMCs but seldom in the histologic mimics, the IHC of RAS Q61R is a useful tool for diagnosing EMC in general pathology laboratories.
Identifiants
pubmed: 33481388
doi: 10.1097/PAS.0000000000001673
pii: 00000478-202107000-00002
pmc: PMC8192334
mid: NIHMS1657564
doi:
Substances chimiques
Biomarkers, Tumor
0
HRAS protein, human
EC 3.6.5.2
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Comparative Study
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
885-894Subventions
Organisme : NCI NIH HHS
ID : P01 CA240239
Pays : United States
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest and Source of Funding: Supported by NIH/NHS 1P01CA240239-01 (W.C.F., P.M.S.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
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