title: Prostate cancer with Paneth cell-like neuroendocrine differentiation has recognizable histomorphology and harbors AURKA gene amplification.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10065.
authors.forename: Kyung
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Public Health, Weill Medical College of Cornell University, New York, NY 10065.
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10065.
authors.forename: Theresa Y
authors.initials: TY
authors.lastname: MacDonald
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI 48109; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqui
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215; Harvard Medical School, Boston, MA 02215.
authors.forename: Huihui
authors.initials: H
authors.lastname: Ye
authors.affiliation: Institute of Pathology, University of Rostock, Rostock, Germany 18057.
authors.forename: Andreas
authors.initials: A
authors.lastname: Erbersdobler
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10065.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Shevchuk
authors.affiliation: 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.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Robinson
authors.affiliation: Division of Urology, Beth Israel Deaconess Medical Center, Boston, MA 02215; Harvard Medical School, Boston, MA 02215.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Sanda
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI 48109; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.affiliation: 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.
authors.forename: Himisha
authors.initials: H
authors.lastname: Beltran
authors.affiliation: 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.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.affiliation: 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.
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Mosquera
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D064096:Aurora Kinase A / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002454:Cell Differentiation; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D019879:Paneth Cells / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: AURKA amplification; MYCN amplification; Neuroendocrine differentiation; Paneth cell–like; Prostate cancer