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ERG gene rearrangements are common in prostatic small cell carcinomas
Open accessAbstract
Small cell carcinoma of the prostate is a rare subtype with an aggressive clinical course. Despite the frequent occurrence of ERG gene rearrangements in acinar carcinoma, the incidence of these rearrangements in prostatic small cell carcinoma is unclear. In addition, molecular markers to distinguish prostatic small cell carcinomas from lung and bladder small cell carcinomas may be clinically useful. We examined the occurrence of ERG gene rearrangements by fluorescence in situ hybridization in prostatic, bladder and lung small cell carcinomas. We also examined the expression of ERG, androgen receptor (AR) and NKX3-1 by immunohistochemistry in prostatic cases. Overall, 45% (10/22) of prostatic small cell carcinoma cases harbored ERG rearrangements, whereas no cases of bladder or lung small cell carcinomas showed ERG rearrangement (0/12 and 0/13, respectively). Of prostatic small cell carcinoma cases, 80% (8/10) showed ERG deletion and 20% (2/10) showed ERG translocation. In 83% (5/6) of prostatic small cell carcinoma cases in which a concurrent conventional prostatic acinar carcinoma component was available for analysis, there was concordance for the presence/absence of ERG gene rearrangement between the different subtypes. ERG, AR and NKX3-1 protein expression was detected in a minority of prostatic small cell carcinoma cases (23, 27 and 18%, respectively), while these markers were positive in the majority of concurrent acinar carcinoma cases (66, 83 and 83%, respectively). The presence of ERG rearrangements in nearly half of the prostatic small cell carcinomas is a similar rate of rearrangement to that found in prostatic acinar carcinomas. Furthermore, the high concordance rate of ERG rearrangement between the small cell and acinar components in a given patient supports a common origin for these two subtypes of prostate cancer. Finally, the absence of ERG rearrangement in bladder or lung small cell carcinomas highlights the utility of detecting ERG rearrangement in small cell carcinomas of unknown primary for establishing prostatic origin.
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Cites
Recurrent Fusion of TMPRSS2 and ETS Transcription Factor Genes in Prostate Cancer
Tomlins, S. A., Rhodes, D. R., Perner, S., Dhanasekaran, S. M., Mehra, R., Sun, X.-W., Varambally, S., Cao, X., Tchinda, J., Kuefer, R., et al. (2005) · Science · doi:10.1126/science.1117679 · Cited by 3,846
Lin, C., Yang, L., Tanasa, B., Hutt, K., Ju, B.-G., Ohgi, K. A., Zhang, J., Rose, D. W., Fu, X.-D., Glass, C. K., et al. (2009) · Cell · doi:10.1016/j.cell.2009.11.030 · Cited by 576
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Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer
Watson, P. A., Arora, V. K., & Sawyers, C. L. (2015) · Nature Reviews Cancer · doi:10.1038/nrc4016 · Cited by 1,536
N-Myc Induces an EZH2-Mediated Transcriptional Program Driving Neuroendocrine Prostate Cancer
Dardenne, E., Beltran, H., Benelli, M., Gayvert, K., Berger, A., Puca, L., Cyrta, J., Sboner, A., Noorzad, Z., MacDonald, T., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.09.005 · Cited by 559
Cellular plasticity and the neuroendocrine phenotype in prostate cancer
Davies, A. H., Beltran, H., & Zoubeidi, A. (2018) · Nature Reviews Urology · doi:10.1038/nrurol.2018.22 · Cited by 431
Zou, M., Toivanen, R., Mitrofanova, A., Floch, N., Hayati, S., Sun, Y., Le Magnen, C., Chester, D., Mostaghel, E. A., Califano, A., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1174 · Cited by 386
Lin, D., Wyatt, A. W., Xue, H., Wang, Y., Dong, X., Haegert, A., Wu, R., Brahmbhatt, S., Mo, F., Jong, L., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2921-t · Cited by 364
Metadata
- Authors
- Lotan, T. L., Gupta, N. S., Wang, W., Toubaji, A., Haffner, M. C., Chaux, A., Hicks, J. L., Meeker, A. K., Bieberich, C. J., De Marzo, A. M., Epstein, J. I., & Netto, G. J.
- Venue
- Modern Pathology
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 24
- Issue
- 6
- Pages
- 820-828
- ISSN
- 0893-3952 (ISSN-L)
- OpenAlex
- W1995113386
- Cited by
- 218
- References
- 2
- FWCI
- 14.10
- Type
- journal article
- Language
- en
- Open access
- bronze
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