TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate

Abstract

Recent studies have shown that most prostate cancers carry the TMPRSS2-ERG gene fusion. Here we evaluated the TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate (n = 12) in comparison with small cell carcinoma of the urinary bladder (n = 12) and lung (n = 11). Fluorescence in situ hybridization demonstrated rearrangement of the ERG gene in 8 cases of prostatic small cell carcinoma (67%), and the rearrangement was associated with deletion of the 5' ERG gene in 7 cases, but rearrangement of the ERG gene was not present in any small cell carcinoma of the urinary bladder or lung. Next we evaluated the TMPRSS2-ERG gene fusion in nude mouse xenografts that were derived from 2 prostatic small cell carcinomas carrying the TMPRSS2-ERG gene fusion. Two transcripts encoded by the TMPRSS2-ERG gene fusion were detected by reverse transcriptase polymerase chain reaction, and DNA sequencing demonstrated that the 2 transcripts were composed of fusions of exon 1 of the TMPRSS2 gene to exon 4 or 5 of the ERG gene. Our study demonstrates the specific presence of TMPRSS2-ERG gene fusion in prostatic small cell carcinoma, which may be helpful in distinguishing small cell carcinoma of prostatic origin from nonprostatic origins. The high prevalence of the TMPRSS2-ERG gene fusion in prostatic small cell carcinoma as well as adenocarcinoma implies that small cell carcinoma may share a common pathogenic pathway with adenocarcinoma in the prostate.

Figure 1

Prostatic small cell carcinoma expresses the TMPRSS2-ERG gene fusion. The tumor shows solid sheets of poorly differentiated carcinoma cells with scant cytoplasm, dense nuclei and inconspicuous nucleoli (A); the tumor cells are immunoreactive for synaptophysin (B); FISH analysis demonstrates rearrangement of the ERG gene associated with deletion of the 5’ ERG gene in one case (C) and without deletion in another case (D).

Figure 2

Bladder small cell carcinoma lacks the TMPRSS2-ERG gene fusion. The tumor cells are poorly differentiated with scant cytoplasm and dense nuclei (A); FISH analysis shows no rearrangement of the ERG gene (B).

Figure 3

Mouse xenograft of prostatic small cell carcinoma expresses the TMPRSS2-ERG gene fusion. The xenograft tumor cells are poorly differentiated with scant cytoplasm and hyperchromatic nuclei (A); the tumor cells are immunoreactive for synaptophysin (B) and chromogranin (C); FISH analysis shows rearrangement of the ERG gene associated with a deletion of the 5’ ERG gene (D); RT-PCR demonstrates two discrete transcripts of the TMPRSS2-ERG gene fusion in two xenografts derived from Cases # 3 (a) and # 9 (b). (E); DNA sequencing demonstrates that the two transcripts are fusions of exon 1 of the TMPRSS2 gene to exon 4 or 5 of the ERG gene (F).