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Gene fusion characterisation of rare aggressive prostate cancer variants-adenosquamous carcinoma, pleomorphic giant-cell carcinoma, and sarcomatoid carcinoma: an analysis of 19 cases
- Source :
- HistopathologyReferences. 77(6)
- Publication Year :
- 2020
-
Abstract
- Aims To evaluate the molecular underpinnings of the rare aggressive prostate cancer variants adenosquamous carcinoma, pleomorphic giant-cell carcinoma, and sarcomatoid carcinoma. Methods and results We retrieved 19 tumours with one or more variant(s), and performed ERG immunohistochemistry, a next-generation sequencing assay targeting recurrent gene fusions, and fluorescence in-situ hybridisation (FISH) for ERG and BRAF. Divergent differentiation included: sarcomatoid carcinoma (n = 10), adenosquamous carcinoma (n = 7), and pleomorphic giant-cell carcinoma (n = 7). Five patients had more than one variant. Four had variants only in metastases. ERG rearrangement was detected in nine (47%, seven via sequencing, showing TMPRSS2-ERG fusions and one GRHL2-ERG fusion, and two via FISH, showing rearrangement via deletion). ERG was immunohistochemically positive in the adenocarcinoma in eight of nine (89%) patients, but was immunohistochemically positive in the variant in only five of nine patients (56%, typically decreased). One patient had a false-positive ERG immunohistochemical result in the sarcomatoid component despite a negative FISH result. Two (11%) harboured BRAF fusions (FAM131A-BRAF and SND1-BRAF). Conclusions ERG fusions are present in these rare prostate cancer variants with a frequency close to that in conventional prostate cancer (9/19, 47%). ERG immunohistochemistry usually detects rearrangement in the adenocarcinoma, but is less sensitive for the variant histology, with weak to negative staining. Adenosquamous and sarcomatoid variants can, particularly, occur together. Molecular assessment may be an additional tool in selected cases to confirm the prostatic origin of unusual tumours. The presence of two BRAF rearrangements suggests that this gene fusion may be enriched in this setting, as RAF kinase fusions have been previously reported in 1-2% of prostate cancers.
- Subjects :
- 0301 basic medicine
Giant Cell Carcinoma
Male
Proto-Oncogene Proteins B-raf
Histology
Oncogene Proteins, Fusion
Adenosquamous carcinoma
Biology
Pathology and Forensic Medicine
Fusion gene
03 medical and health sciences
Prostate cancer
Carcinoma, Adenosquamous
0302 clinical medicine
Transcriptional Regulator ERG
medicine
Carcinoma
Humans
Neoplasm Metastasis
Sarcomatoid carcinoma
Carcinoma, Renal Cell
In Situ Hybridization, Fluorescence
Aged
Aged, 80 and over
Gene Rearrangement
Serine Endopeptidases
High-Throughput Nucleotide Sequencing
Prostatic Neoplasms
Carcinoma, Giant Cell
General Medicine
Middle Aged
medicine.disease
Immunohistochemistry
DNA-Binding Proteins
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
Adenocarcinoma
Gene Fusion
Erg
Transcription Factors
Subjects
Details
- ISSN :
- 13652559
- Volume :
- 77
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- HistopathologyReferences
- Accession number :
- edsair.doi.dedup.....50bc047dbc8feb75aaf17edd6a23915c