title: Frequent TMPRSS2-ERG rearrangement in prostatic small cell carcinoma detected by fluorescence in situ hybridization: the superiority of fluorescence in situ hybridization over ERG immunohistochemistry.
abstract: Small cell carcinoma of the prostate is both morphologically and immunohistochemically similar to small cell carcinoma of other organs such as the urinary bladder or lung. TMPRSS2-ERG gene fusion appears to be a highly specific alteration in prostatic carcinoma that is frequently shared by small cell carcinoma. In adenocarcinoma, immunohistochemistry for the ERG protein product has been reported to correlate well with the presence of the gene fusion, although in prostatic small cell carcinoma, this relationship is not completely understood. We evaluated 54 cases of small cell carcinoma of the prostate and compared TMPRSS2-ERG gene fusion status by fluorescence in situ hybridization (FISH) to immunohistochemical staining with antibody to ERG. Of 54 cases of prostatic small cell carcinoma, 26 (48%) were positive for TMPRSS2-ERG gene fusion by FISH and 12 (22%) showed overexpression of ERG protein by immunohistochemistry. Of the 26 cases positive by FISH, 11 were also positive for ERG protein by immunohistochemistry. One tumor was positive by immunohistochemistry but negative by FISH. Urinary bladder small cell carcinoma (n = 25) showed negative results by both methods; however, 2 of 14 small cell carcinomas of other organs (lung, head, and neck) showed positive immunohistochemistry but negative FISH. Positive staining for ERG by immunohistochemistry is present in a subset of prostatic small cell carcinomas and correlates with the presence of TMPRSS2-ERG gene fusion. Therefore, it may be useful in confirming prostatic origin when molecular testing is not accessible. However, sensitivity and specificity of ERG immunohistochemistry in small cell carcinoma are decreased compared to FISH.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Schelling
authors.forename: Sean R
authors.initials: SR
authors.lastname: Williamson
authors.forename: Shaobo
authors.initials: S
authors.lastname: Zhang
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Yao
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Wang
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.forename: Robert E
authors.initials: RE
authors.lastname: Emerson
authors.forename: Muhammad T
authors.initials: MT
authors.lastname: Idrees
authors.forename: Adeboye O
authors.initials: AO
authors.lastname: Osunkoya
authors.forename: Yan-Gao
authors.initials: YG
authors.lastname: Man
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Maclennan
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Baldridge
authors.forename: Eva
authors.initials: E
authors.lastname: Compérat
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000378:metabolism; D000071230:Transcriptional Regulator ERG
chemical_list: D014408:Biomarkers, Tumor; C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
keywords: Fluorescence in situ hybridization; Histogenesis; Molecular genetics; Neuroendocrine tumor; Prostate; Small cell carcinoma; TMPRSS2-ERG rearrangement; Tumor of unknown origin