Faculty Collaboration Database

Genomic Alterations in Undifferentiated Malignant Tumors with Rhabdoid Phenotype and Loss of BRG1 Immunoexpression Identified by Fine Needle Aspirates. Acta Cytol 2019;63(5):438-444

Date

06/24/2019

Pubmed ID

31230044

DOI

10.1159/000500684

Scopus ID

2-s2.0-85068601882 (requires institutional sign-in at Scopus site)   4 Citations

Abstract

OBJECTIVE: Evidence shows that the switch/sucrose nonfermenting chromatin remodeling complex plays a critical role in DNA repair, cancer progression and dedifferentiation. BRG1 is one of its key catalytic subunits. While the loss of BRG1 expression by immunocytochemistry has been identified in a subset of malignancies arising in various sites with undifferentiated/rhabdoid morphology and poor prognosis, the underlying basis for its loss is unclear.

METHODS: A retrospective search was conducted in our cytopathology archive for undifferentiated malignant tumors with rhabdoid phenotype and BRG1 loss. Clinical information was obtained from electronic medical records. Next-generation sequencing was performed following macro-dissection of paraffin-embedded cellblock tissue.

RESULTS: Three cases were identified; all presented with widely metastatic disease with no previously diagnosed primary malignancy, and subsequently died within 6 months of initial presentation. Cytologically, the aspirates showed dyshesive and undifferentiated cells with rhabdoid features. Extensive immunocytochemical workup demonstrated immunoreactivity with vimentin only and could not establish a specific lineage. BRG1 expression was absent, while INI1 expression was retained. Two cases harbored deleterious mutations in BRG1/SMARCA4. Pathogenic mutations in TP53 were identified in all tumors.

CONCLUSIONS: BRG1 deficiency reflects underlying mutation in SMARCA4 gene in some but not all cases, suggesting that additional mechanisms may be causing BRG1 silencing. Pathogenic mutations in TP53 in all tumors are consistent with their highly aggressive nature. Recognizing the cytomorphology of this group of neoplasms and confirming their BRG1-deficient status by immunocytochemistry not only has prognostic implications, but may also impart potentially therapeutic value in the near future.

Author List

Mei L, Alikhan M, Mujacic I, Parilla M, Antic T

Author

Ling Mei MD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Biomarkers, Tumor
Biopsy, Fine-Needle
Cell Differentiation
DNA Helicases
DNA Mutational Analysis
Fatal Outcome
Female
Genetic Predisposition to Disease
Humans
Immunohistochemistry
Lung Neoplasms
Male
Middle Aged
Mutation
Nuclear Proteins
Phenotype
Predictive Value of Tests
Retrospective Studies
Rhabdoid Tumor
Submandibular Gland Neoplasms
Transcription Factors
Treatment Outcome
Tumor Suppressor Protein p53