Increased androgen receptor gene copy number is associated with TMPRSS2-ERG rearrangement in prostatic small cell carcinoma.
Small cell carcinoma of the prostate (PSCC) is a highly aggressive malignancy that often develops in patients previously treated with hormonal therapy for metastatic prostatic acinar adenocarcinoma. The TMPRSS2-ERG gene rearrangement is highly specific for prostate cancer and shared by PSCC; however, the role of androgen receptor (AR) gene alterations and interaction with TMPRSS2-ERG rearrangement are incompletely understood in PSCC. Sixty-one cases of PSCC were examined for AR gene copy number and TMPRSS2-ERG rearrangement by fluorescence in situ hybridization (FISH) and AR protein expression by immunohistochemistry. Of 61 cases of PSCC, 51% (31/61) demonstrated increased AR gene copy number (FISH+), 54% (33/61) were positive for TMPRSS2-ERG gene fusion, and 38% (23/61) showed AR protein expression. Of the 31 AR FISH+ cases, 23 also showed TMPRSS2-ERG gene fusion, and 16 expressed AR protein. Of the 33 cases with TMPRSS2-ERG fusion, 28 were AR FISH+ or expressed AR protein. Statistically significant correlations were observed between AR gene copy number or AR protein expression and TMPRSS2-ERG gene fusion (P = 0.001 and P = 0.03, respectively). In summary, high AR gene copy number emerges during the development of PSCC, often in association with TMPRSS2-ERG rearrangement. This potential mechanism warrants further study. Improvement will come from understanding the biology of the disease and integrating new therapies into the treatment of this rare and aggressive tumor.
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Lisha
L
Wang
Department of Pathology, Henry Ford Health System, Detroit, Michigan.
Sean R
SR
Williamson
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Shaobo
S
Zhang
Department of Pathology, University of California at Los Angeles, Los Angeles, California.
Jiaoti
J
Huang
Institute of Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona, Italy.
Rodolfo
R
Montironi
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Darrell D
DD
Davison
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Mingsheng
M
Wang
Pathline Laboratories, Ramsey, New Jersey.
Jorge L
JL
Yao
Department of Pathology, Cordoba University, Cordoba, Spain.
Antonio
A
Lopez-Beltran
Department of Pathology, Emory University, Atlanta, Georgia.
Adeboye O
AO
Osunkoya
Department of Pathology, Case Western Reserve University, Cleveland, Ohio.
Gregory T
GT
MacLennan
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Lee Ann
LA
Baldridge
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Xiang
X
Du
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Liang
L
Cheng
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000473:pathology; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000032:analysis / Q000235:genetics*; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011944:Receptors, Androgen / Q000032:analysis / Q000235:genetics*
C410798:AR protein, human; D015514:Oncogene Proteins, Fusion; D011944:Receptors, Androgen; C515553:TMPRSS2-ERG fusion protein, human
TMPRSS2-ERG rearrangement; androgen receptor; gene copy number; molecular cytogenetics, fluorescence in situ hybridization; prostate; small cell carcinoma; tumorigenesis