title: Basal cell carcinoma of the prostate is an aggressive tumor with frequent loss of PTEN expression and overexpression of EGFR.
abstract: Basal cell carcinoma (also referred to as adenoid cystic carcinoma) is a rare tumor of the prostate. Although largely characterized as indolent, poor outcomes have been reported in a considerable fraction of cases. As yet, optimum treatment strategies for this cancer have not been developed. This study investigates protein expression of common or potential molecular therapeutic targets and reports on the clinicopathological features of 9 new cases. We evaluated the expression of ERBB2, KIT, androgen receptor, PTEN, EGFR, ERG, and p53 via immunohistochemistry. We also examined EGFR amplification and TMPRSS2-ERG gene rearrangement by fluorescence in situ hybridization. The mean clinical follow-up was 44 months. We found that basal cell carcinoma behaved aggressively with almost one-half of the cases displaying high-risk pathologic features or local recurrence (44%). One patient died as a result of metastatic disease. The most consistent abnormalities included a loss of PTEN expression (56% of cases) and EGFR overexpression (67% of cases). EGFR overexpression occurred in the absence of gene amplification. The TMPRSS2-ERG rearrangement was not detected in any of the tumors studied, nor was ERG protein positivity identified by immunostaining. In addition, ERBB2, KIT, p53, and androgen receptor expressions were either absent or showed only weak, limited reactivity. Our results suggest that there is a high morbidity associated with this tumor, and more intense follow-up and additional treatment may be indicated. Furthermore, targeted therapies directed against the EGFR and PTEN proteins or their constitutive pathways may be promising for future clinical management.
authors: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, 46202, IN.
authors: Novae B
authors: NB
authors: Simper
authors: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, 46202, IN.
authors: Carol L
authors: CL
authors: Jones
authors: Department of Pathology, Case Western Reserve University, Cleveland, 44106, OH.
authors: Gregory T
authors: GT
authors: MacLennan
authors: Institute of Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of the Marche Region and United Hospitals, Ancona, 60126, Italy.
authors: Rodolfo
authors: R
authors: Montironi
authors: Department of Pathology, Henry Ford Health System, Detroit, 48202, MI.
authors: Sean R
authors: SR
authors: Williamson
authors: Department of Pathology, Emory University, Atlanta, 30322, GA.
authors: Adeboye O
authors: AO
authors: Osunkoya
authors: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, 46202, IN.
authors: Mingsheng
authors: M
authors: Wang
authors: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, 46202, IN.
authors: Shaobo
authors: S
authors: Zhang
authors: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, 46202, IN.
authors: David J
authors: DJ
authors: Grignon
authors: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, 46202, IN.
authors: John N
authors: JN
authors: Eble
authors: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, 46202, IN.
authors: Thu
authors: T
authors: Tran
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200433, China.
authors: Lisha
authors: L
authors: Wang
authors: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, 46202, IN.
authors: Lee Ann
authors: LA
authors: Baldrige
authors: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, 46202, IN. Electronic address: liang_cheng@yahoo.com.
authors: Liang
authors: L
authors: Cheng
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005784:Gene Amplification / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism
chemical_list: C410798:AR protein, human; D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; C512478:EGFR protein, human; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Basal cell carcinoma; Epidermal growth factor receptor (EGFR); Fluorescence in situ hybridization (FISH); Immunohistochemistry; Molecular genetics; Phosphate and tensin homolog (PTEN); Prostate