Biomarker immunoprofile and molecular characteristics in salivary duct carcinoma: clinicopathological and prognostic implications
| Autor: | Petr Steiner, Alena Skálová, Petr Martinek, Martina Baněčková, Andrle Pavel, Thalita Santana, Petr Grossmann |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Pathology and Forensic Medicine Salivary duct carcinoma 03 medical and health sciences 0302 clinical medicine CDKN2A Gene duplication Biomarkers Tumor ERBB2 Gene Amplification medicine Humans Salivary Ducts HRAS Aged Sequence Deletion Aged 80 and over medicine.diagnostic_test business.industry Homozygote Apocrine High-Throughput Nucleotide Sequencing Middle Aged Salivary Gland Neoplasms medicine.disease Carcinoma Ductal 030104 developmental biology 030220 oncology & carcinogenesis Mutation Cancer research Female Salivary gland neoplasm business Fluorescence in situ hybridization |
| Zdroj: | Human Pathology. 93:37-47 |
| ISSN: | 0046-8177 |
| Popis: | Summary Salivary duct carcinoma (SDC) is one of the most aggressive salivary gland tumors, and prognosis remains poor for most patients. The aim of this study was to investigate the prognostic implications of biomarker immunoprofile in a cohort of SDC and to identify molecular characteristics through next-generation sequencing (NGS) in a subset of cases. Clinicopathological and follow-up information of 25 cases diagnosed as SDC was collected. Immunoexpression of AR, HER-2/neu, GATA3, CK5/6, and MIB1 was analyzed, and ERBB2 (HER-2/Neu) gene amplification was investigated by fluorescence in situ hybridization. Cases were classified under the “SDC revised classification system.” Eight SDC cases were analyzed by targeted NGS for detection of gene fusions and variants. Overall survival and disease-free survival were analyzed with Kaplan-Meier curves and Cox regression. Most cases expressed AR (100%), GATA3 (73%), and CK5/6 (76.5%), and 42% expressed HER-2/neu. ERBB2 gene amplification was proven by fluorescence in situ hybridization in 7 of 15 (46%) cases. Apocrine HER2 (AR+/HER2+) subtype was significantly associated with lower overall survival (P = .05). NGS analysis revealed 9 pathogenic mutations in 7 SDC cases, and the most frequently mutated gene was HRAS (4/9) followed by PIK3CA (2/9) and TP53 (2/9). One case (1/9) presented homozygous deletion of locus 9p21 (CDKN2A), and another case (1/9) showed MDM2 amplification. In conclusion, we demonstrated that Apocrine HER2 (AR+/HER2+) is a potential biomarker of poor outcome in SDC. Furthermore, NGS analysis revealed recurrent mutations in SDC. |
| Databáze: | OpenAIRE |
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