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      Prostate cancer with Paneth cell-like neuroendocrine differentiation has recognizable histomorphology and harbors AURKA gene amplification.

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          Abstract

          Aurora kinase A (AURKA) gene amplification has been documented in 67% of hormone-naive prostate cancer cases that progress to a highly aggressive variant of castrate-resistant disease, clinically referred to as "neuroendocrine" prostate cancer, "small cell" prostate carcinoma, or "anaplastic" prostate cancer. Therefore, AURKA amplification is a potential prognostic biomarker that may help to identify patients with prostate cancer who are at high risk for developing castrate-resistant disease with clinical features of small cell carcinoma. Furthermore, AURKA inhibitors are currently being tested in clinical trials. In a previous study, we found AURKA amplification in 6 cases of prostate cancer with Paneth cell-like cells. This morphologic pattern has been suggested to represent low-grade neuroendocrine differentiation (NED) with generally favorable prognosis. We sought to investigate the frequency of AURKA amplification and the histologic characteristics of prostate cancer with Paneth cell-like NED. Twenty-five cases from 172 prostatectomies were evaluated for the presence of 18 morphologic features and AURKA amplification. Most prostate cancers with Paneth cell-like NED had macronucleoli (92%), basophilic appearance (88%), perineural invasion (72%), and nuclear stratification (76%). The frequency of AURKA amplification was 45%, present throughout the examined tumor nodule including areas without Paneth cell-like cells. When histologically similar cases with and without AURKA amplification were compared, this gene alteration was associated with larger extent of Paneth cell-like NED identified at magnification ×20 (P = .015), higher percentage of Paneth cell-like NED throughout the tumor nodule (P = .033), ductal features (P = .02), and higher overall Gleason grade (P = .039). AURKA amplification was not associated with age, serum prostate specific antigen, or tumor stage. The high frequency of AURKA amplification (45%) in localized prostate cancer with Paneth cell-like NED and its potential prognostic significance warrant further investigation.

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          Author and article information

          Journal
          Hum. Pathol.
          Human pathology
          Elsevier BV
          1532-8392
          0046-8177
          Oct 2014
          : 45
          : 10
          Affiliations
          [1 ] Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10065.
          [2 ] Department of Public Health, Weill Medical College of Cornell University, New York, NY 10065.
          [3 ] Department of Pathology, University of Michigan, Ann Arbor, MI 48109; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.
          [4 ] Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215; Harvard Medical School, Boston, MA 02215.
          [5 ] Institute of Pathology, University of Rostock, Rostock, Germany 18057.
          [6 ] Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10065; Department of Urology, Weill Medical College of Cornell University, New York, NY 10065; Institute for Precision Medicine of Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY 10065.
          [7 ] Division of Urology, Beth Israel Deaconess Medical Center, Boston, MA 02215; Harvard Medical School, Boston, MA 02215.
          [8 ] Department of Medicine, Division of Hematology and Oncology, Weill Medical College of Cornell University, New York, NY 10065; Institute for Precision Medicine of Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY 10065.
          [9 ] Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10065; Institute for Precision Medicine of Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY 10065.
          [10 ] Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10065; Institute for Precision Medicine of Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY 10065. Electronic address: jmm9018@med.cornell.edu.
          Article
          S0046-8177(14)00247-0 NIHMS656659
          10.1016/j.humpath.2014.06.008
          4414025
          25128228
          5a228412-1491-4aff-84e9-3e83cec5b121
          History

          AURKA amplification,MYCN amplification,Neuroendocrine differentiation,Paneth cell–like,Prostate cancer

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