title: ERG gene rearrangements are common in prostatic small cell carcinomas.
abstract: 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.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Lotan
authors.forename: Nilesh S
authors.initials: NS
authors.lastname: Gupta
authors.forename: Wenle
authors.initials: W
authors.lastname: Wang
authors.forename: Antoun
authors.initials: A
authors.lastname: Toubaji
authors.forename: Michael C
authors.initials: MC
authors.lastname: Haffner
authors.forename: Alcides
authors.initials: A
authors.lastname: Chaux
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Hicks
authors.forename: Alan K
authors.initials: AK
authors.lastname: Meeker
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Bieberich
authors.forename: Angelo M
authors.initials: AM
authors.lastname: De Marzo
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004273:DNA, Neoplasm / Q000032:analysis; D015321:Gene Rearrangement; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000071230:Transcriptional Regulator ERG
chemical_list: D004273:DNA, Neoplasm; C072312:ERG protein, human; D018398:Homeodomain Proteins; C491178:NKX3-1 protein, human; D011944:Receptors, Androgen; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG