The value of GLI1 and p16 immunohistochemistry in the premolecular screening for GLI1-altered mesenchymal neoplasms
Machado I, Agaimy A, Giner F, Navarro S, Michal M, Bridge J, Claramunt R, López-Guerrero JA, Alcacer J, Linos K, Llombart-Bosch A (2023)
Publication Type: Journal article
Publication year: 2023
Journal
DOI: 10.1007/s00428-023-03687-3
Abstract
Mesenchymal neoplasms with GLI1 alterations have recently been reported in several anatomic locations. Their morphology and immunohistochemistry (IHC) are nonspecific, making their recognition a true challenge. To assess the diagnostic value of GLI1 and p16 IHC for identifying GLI1-altered neoplasms, we evaluated 12 such neoplasms (6 GLI1-amplified and 6 with GLI1-fusions) using the GLI1 IHC. Additionally, we evaluated some of their morphological and molecular mimickers, including glomangiomas, Ewing sarcomas (ES), myxoid liposarcomas, and MDM2/CDK4-amplified sarcomas (well-differentiated liposarcoma/WDLPS, dedifferentiated liposarcoma/DDLPS, and intimal sarcoma). All successfully tested GLI1-altered tumors (11/11) demonstrated at least moderate/strong nuclear and/or cytoplasmic GLI1 IHC positivity. GLI1-amplified tumors exhibited a moderate/strong predominantly nuclear staining, compared to a moderate, patchy, and predominantly cytoplasmic GLI1 positivity in GLI1-fusion tumors. Among their mimics, GLI1 immunoreactivity, either cytoplasmic or nuclear, was observed in intimal sarcoma (3/3) and WDLPS/DDLPS (22/25). GLI1 IHC demonstrated 92% sensitivity and 90.8% specificity in diagnosing GLI1-altered neoplasms. Strong/moderate nuclear/cytoplasmic p16 immunoexpression was noted in all GLI1-amplified tumors compared to none of fused cases. Overall, the GLI1/p16 combination demonstrated a sensitivity and specificity of 100% and 93% for GLI1-amplified tumors. In conclusion, we confirm that GLI1 IHC represents a good, quick, and cheap helpful screening tool. The inclusion of p16 may aid in pre-screening for potential GLI1-amplified neoplasms and provide insights on which tumors warrant further molecular testing.
Authors with CRIS profile
Involved external institutions
Valencia Oncology Institute Foundation / Fundación Instituto Valenciano de Oncología / Fundació Institut Valencià d’Oncologia (IVO)
Spain (ES)
Quirónsalud Valencia Hospital
Spain (ES)
University of València / Universitat de València
Spain (ES)
Fakultní Nemocnice Plzeň
Czech Republic (CZ)
University of Nebraska Medical Center (UNMC)
United States (USA) (US)
Memorial Sloan Kettering Cancer Center
United States (USA) (US)
Spain (ES)
Quirónsalud Valencia Hospital
Spain (ES)
University of València / Universitat de València
Spain (ES)
Fakultní Nemocnice Plzeň
Czech Republic (CZ)
University of Nebraska Medical Center (UNMC)
United States (USA) (US)
Memorial Sloan Kettering Cancer Center
United States (USA) (US)
How to cite
APA:
Machado, I., Agaimy, A., Giner, F., Navarro, S., Michal, M., Bridge, J.,... Llombart-Bosch, A. (2023). The value of GLI1 and p16 immunohistochemistry in the premolecular screening for GLI1-altered mesenchymal neoplasms. Virchows Archiv. https://doi.org/10.1007/s00428-023-03687-3
MLA:
Machado, Isidro, et al. "The value of GLI1 and p16 immunohistochemistry in the premolecular screening for GLI1-altered mesenchymal neoplasms." Virchows Archiv (2023).
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