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

Lindsay A. Schelling, Sean R. Williamson, Shaobo Zhang, Jorge L. Yao, Mingsheng Wang, Jiaoti Huang, Rodolfo Montironi, Antonio Lopez-Beltran, Robert Emerson, Muhammad Idrees, Adeboye O. Osunkoya, Yan Gao Man, Gregory T. Maclennan, Lee Ann Baldridge, Eva Compérat, Liang Cheng

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Summary 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.

Original languageEnglish
Pages (from-to)2227-2233
Number of pages7
JournalHuman Pathology
Volume44
Issue number10
DOIs
StatePublished - Oct 2013

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Small Cell Carcinoma
Fluorescence In Situ Hybridization
Immunohistochemistry
Gene Fusion
Prostate
Urinary Bladder
Staining and Labeling
Lung
Proteins
Adenocarcinoma
Neck
Head
Carcinoma
Sensitivity and Specificity

Keywords

  • Fluorescence in situ hybridization
  • Histogenesis Neuroendocrine tumor
  • Molecular genetics
  • Prostate
  • Small cell carcinoma
  • TMPRSS2-ERG rearrangement
  • Tumor of unknown origin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

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. / Schelling, Lindsay A.; Williamson, Sean R.; Zhang, Shaobo; Yao, Jorge L.; Wang, Mingsheng; Huang, Jiaoti; Montironi, Rodolfo; Lopez-Beltran, Antonio; Emerson, Robert; Idrees, Muhammad; Osunkoya, Adeboye O.; Man, Yan Gao; Maclennan, Gregory T.; Baldridge, Lee Ann; Compérat, Eva; Cheng, Liang.

In: Human Pathology, Vol. 44, No. 10, 10.2013, p. 2227-2233.

Research output: Contribution to journalArticle

Schelling, Lindsay A. ; Williamson, Sean R. ; Zhang, Shaobo ; Yao, Jorge L. ; Wang, Mingsheng ; Huang, Jiaoti ; Montironi, Rodolfo ; Lopez-Beltran, Antonio ; Emerson, Robert ; Idrees, Muhammad ; Osunkoya, Adeboye O. ; Man, Yan Gao ; Maclennan, Gregory T. ; Baldridge, Lee Ann ; Compérat, Eva ; Cheng, Liang. / 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. In: Human Pathology. 2013 ; Vol. 44, No. 10. pp. 2227-2233.
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abstract = "Summary 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.",
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T1 - Frequent TMPRSS2-ERG rearrangement in prostatic small cell carcinoma detected by fluorescence in situ hybridization

T2 - The superiority of fluorescence in situ hybridization over ERG immunohistochemistry

AU - Schelling, Lindsay A.

AU - Williamson, Sean R.

AU - Zhang, Shaobo

AU - Yao, Jorge L.

AU - Wang, Mingsheng

AU - Huang, Jiaoti

AU - Montironi, Rodolfo

AU - Lopez-Beltran, Antonio

AU - Emerson, Robert

AU - Idrees, Muhammad

AU - Osunkoya, Adeboye O.

AU - Man, Yan Gao

AU - Maclennan, Gregory T.

AU - Baldridge, Lee Ann

AU - Compérat, Eva

AU - Cheng, Liang

PY - 2013/10

Y1 - 2013/10

N2 - Summary 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.

AB - Summary 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.

KW - Fluorescence in situ hybridization

KW - Histogenesis Neuroendocrine tumor

KW - Molecular genetics

KW - Prostate

KW - Small cell carcinoma

KW - TMPRSS2-ERG rearrangement

KW - Tumor of unknown origin

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