[994] Prostate Cancer with Paneth Cell-Like Neuroendocrine Differentiation Has Distinct Histomorphology and Harbors AURKA Gene Amplification

Kyung Park, Theresa MacDonald, Zhengming Chen, Javed Siddiqui, Huihui Ye, Andreas Erbersdobler, Maria M Shevchuk, Brian D Robinson, Mark A Rubin, Juan Miguel Mosquera. Weill Medical College of Cornell University, New York, NY; University of Michigan, Ann Arbor, MI; Beth Israel Deaconess Medical Center, Boston, MA; University of Rostock, Rostock, Germany

Background: With a prevalence of ∼10%, paneth cell-like change in prostate cancer (PCA) has been suggested to represent low-grade neuroendocrine differentiation with favorable prognosis. The prevalence of Aurora kinase A (AURKA) amplification in unselected cohorts of primary PCA is 5%, in contrast to 65% in neuroendocrine PCA (NEPC). Further, AURKA amplification has been documented in PCA cases that progress to NECP. We sought to investigate AURKA amplification and histologic characteristics of PCA with Paneth cell-like neuroendocrine differentiation (PCLNED).
Design: 24 cases of localized PCA with PCLNED were studied. Tumors were assessed for presence or absence of 18 morphological features, and for ERG translocation and AURKA amplification by immunohistochemistry and fluorescence in situ hybridization, respectively. The extent of PCLNED and Gleason patterns 4 and 5 were assessed in identified tumor nodules. Statistical analysis was performed to look for significant associations between AURKA amplification and clinical characteristics.
Results: Most PCA with PCLNED had a basophilic appearance (88%; 21/24), macronucleoli (96%; 23/24), and perineural invasion (75%; 18/24). All three morphological features were seen in 62.5% of cases (15/24). Extent of PCLNED ranged from 0.1 to 40% at 20x in the region with most Paneth cell-like change. Among assessable cases, 58%(14/24) had ERG translocation and 43% (9/21) harbored AURKA amplification, which was present throughout tumor nodule including areas without PCLNED. When cases with and without AURKA amplification were compared, AURKA amplification was associated with ductal features (p=0.046), higher percentage of Gleason pattern 4 and 5 (p=0.011), and larger extent of PCLNED identified at 20x magnification (p=0.025). AURKA amplification was not associated with age, serum PSA, overall Gleason grade, or tumor stage.
Conclusions: Most cases of PCA with PCLNED can be identified on H&E. Given the potential clinical implications of AURKA amplification in localized PCA, the high frequency of AURKA amplification (43%) that we have identified in PCA with PCLNED should be further studied as this may identify patients at risk for progression to NEPC. This work also suggests that PCLNED may not be a feature of low-grade prostate cancer.
Category: Genitourinary (including renal tumors)

Monday, March 4, 2013 11:45 AM

Proffered Papers: Section A, Monday Morning

 

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