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

Kyung Park; Zhengming Chen; Theresa Y MacDonald; Javed Siddiqui; Huihui Ye; Andreas Erbersdobler; Maria M Shevchuk; Brian D Robinson; Martin G Sanda; Arul M Chinnaiyan; Himisha Beltran; Mark A Rubin; Juan Miguel Mosquera

doi:10.1016/j.humpath.2014.06.008

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

Hum Pathol. 2014 Oct;45(10):2136-43. doi: 10.1016/j.humpath.2014.06.008. Epub 2014 Jun 26.

Authors

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.

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.

Keywords: AURKA amplification; MYCN amplification; Neuroendocrine differentiation; Paneth cell–like; Prostate cancer.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adenocarcinoma / genetics*
Adenocarcinoma / pathology*
Aged
Aged, 80 and over
Aurora Kinase A / genetics*
Biomarkers, Tumor / analysis
Biomarkers, Tumor / genetics
Cell Differentiation
Female
Gene Amplification
Humans
In Situ Hybridization, Fluorescence
Male
Middle Aged
Paneth Cells / pathology
Prostatic Neoplasms / genetics*
Prostatic Neoplasms / pathology*

Substances

Biomarkers, Tumor
AURKA protein, human
Aurora Kinase A

Abstract

Publication types

MeSH terms

Substances

Grants and funding