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Basal Cell Carcinoma of the Prostate is an Aggressive Tumor with Frequent Loss of PTEN Expression and Overexpression of EGFR

2015-02-26 00:01:44

Human Pathology; 26 FEB 2015; DOI: 10.1016/j.humpath.2015.02.004



Novae B. Simper, M.D., Carol L. Jones, M.D., Gregory T. MacLennan, M.D., Rodolfo Montironi, M.D., Sean R. Williamson, M.D., Adeboye O. Osunkoya, M.D., Mingsheng Wang, M.D., Shaobo Zhang, M.D., David J. Grignon, M.D., John N. Eble, M.D., Thu Tran, M.D., Lisha Wang, M.D., Lee Ann Baldrige, BA, HT (AJCP), Liang Cheng, M.D.



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 clinicopathologic features of nine new cases. We evaluated the expression of ERBB2, KIT, androgen receptor, PTEN, EGFR, ERG, and TP53 via immunohistochemistry. We also examined EGFR amplification and TMPRSS2-ERG gene rearrangement by fluorescence in situ hybridization. The mean clinical followup was 44 months. We found that basal cell carcinoma behaved aggressively with almost half of 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. Additionally, ERBB2, KIT, TP53, and androgen receptor expression 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. Also, targeted therapies directed against the EGFR and PTEN proteins or their constitutive pathways may be promising for future clinical management.



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Key Words



Basal cell carcinoma | adenoid cystic carcinoma | prostate | phosphate and tensin homolog (PTEN) | epidermal growth factor receptor (EGFR) | molecular genetics | immunohistochemistry | fluorescence in situ hybridization (FISH)