TMPRSS2-ERG gene fusion in metastatic prostate cancers: A study of fine needle aspiration specimens

Objective To investigate diagnostic values of the detection of TMPRSS2-ERG gene fusion in metastatic prostate cancer. Methods A total of 32 fine needle aspiration (FNA) specimens of metastatic prostate carcinomas were retrieved from the pathology files at MD Anderson Cancer Center. The metastatic sites included the pelvic and remote lymph nodes, liver, bone, and thyroid gland. Immunohistochemical staining for PSA, PAP, synaptophysin, chromogranin A was performed. TMPRSS2-ERG genefusion was evaluated on sections of cell blocks by fluorescence in situ hybridization (FISH) usingERG gene break-apart probes. Results The mean age of the patients was 67 years. Twenty-six patients had a previous history of prostatic adenocarcinoma, while 6 patients presented initially with metastasis. In 11 patients, the metastatic lesions showed characteristic features of small cell carcinoma (SCC) and were positive for synaptophysin (9/9), chromogranin A (7/8), but negative for prostatic specific antigen (7/7). FISH analysis demonstrated a rearrangement of ERG gene in 10of 32 cases (31.3%), and the rearrangement was associated with deletion of the 5' ERG gene in 6 cases. In addition, the copy number of ERG rearrangement gene locus was increased in 8 cases. Among the 11 cases with SCC features, a rearrangement of ERG gene was present in 5 cases, of which a deletion of the 5' ERG gene and increased copy number were seen in 3 cases. Conclusions TMPRSS2-ERG gene fusion can be evaluated in FNA specimens of metastatic prostate cancer. Metastatic prostate cancers have a high prevalence of TMPRSS2-ERG gene fusion along with a frequent copy number increaseof ERG gene. TMPRSS2-ERG gene fusion persists in metastatic prostate cancers and even in those with poorly differentiated SCC features. Therefore.