Correlation between Decipher® neuroendocrine signatures and histopathological features of neuroendocrine cancer of the prostate

Committee/Faculty

Co-Author(s)

SR

Siddharth Ramanathan, n/a

Medical Student
Oakland University William Beaumont School of Medicine
bloomfield hills, Michigan, United States

Disclosure: Disclosure information not submitted.
SR

Sadhna Ramanathan

B.Sc
Genesis Care
west bloomfield, Michigan, United States

Disclosure: Disclosure information not submitted.

Presenting Author(s)

AM

Alvaro Martinez

M.D.
Genesicare
west bloomfield, Michigan, United States

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Co-Author(s)

NS

Nathan Shen, n/a

Medical Student
Central Michigan University School of Medicine
west bloomfield, Michigan, United States

Disclosure: Disclosure information not submitted.
ZG

Zachary Gerndt, n/a

B.Sc
Genesis Care
west bloomfield, Michigan, United States

Disclosure: Disclosure information not submitted.
AK

Andrew Korman, n/a

B.S
Comprehensive Urology
Royal oak, Michigan, United States

Disclosure: Disclosure information not submitted.
KW

Kirk Wojno

M.D.
Comprehensive Urology
royal oak, Michigan, United States

Disclosure: Disclosure information not submitted.
HK

Howard Korman

M.D.
Comprehensive Urology
royal oak, Michigan, United States

Disclosure: Disclosure information not submitted.
ML

Michael Levin

M.D.
comprehensive urology
royal oak, Michigan, United States

Disclosure: Disclosure information not submitted.
MG

Michael Ghilezan

M.D.
Genesiscare
west bloomfield, Michigan, United States

Disclosure: Disclosure information not submitted.
SB

Savitha Balaraman

M.D.
Michigan Healthcare Professionals
royal oak, Michigan, United States

Disclosure: Disclosure information not submitted.

Purpose: Neuroendocrine prostate cancer (NEPC) is a rare, extremely aggressive malignancy with a high propensity for metastasis and is often resistant to androgen deprivation therapy. Denovo NEPCs typically present with early metastases to the viscera, bone, and brain. Distinguishing these cancers from other high grade prostatic neoplasms is obfuscated by the myriad of shared features on histopathologic specimens, including poor differentiation, high nuclear to cytoplasmic ratio, and high mitotic rate, among many others. We analyzed histopathology slides for 29 patients with neuroendocrine Decipher® GRID signatures to determine the clinical utility of this tool in patients with intermediate and high Gleason grade prostate cancer.

Methodology: Histopathology slides from 29 patients who were positive for unique neuroendocrine signatures on the Decipher® genome-wide RNA GRID assay were retrospectively analyzed. Presence of high grade adenocarcinoma or NEPC features on histology were assessed. A concordance analysis between the Decipher® GRID signature and histopathology was conducted to determine if neuroendocrine features were present on initial biopsy and missed (misdiagnosis), were not present on initial biopsy (tumor feature), or were present on initial biopsy and recorded as neuroendocrine NEPC (correct identification).

Results: Tumors in 1/29 (3.4%) of patients who had positive neuroendocrine or small cell signatures on Decipher® genomic assay were initially identified as high grade prostatic adenocarcinoma based on histopathological features at the time of diagnosis. None of the 28 patients not initially diagnosed with NEPC had neuroendocrine features on histopathology review. On diagnostic biopsy, 12/29 (41.4%) patients had perineural invasion and 2/29 (6.9%) had extra prostatic extension. Five patients had metastatic disease confirmed within 3 weeks of diagnosing the primary prostate cancer.

Conclusions: Our review found an extremely poor concordance rate between histopathological features and Decipher® genomic GRID testing, where more than 95% of NEPC were missed on histopathological analysis alone. The high rate of perineural invasion and metastatic disease support the aggressive features of NEPC described in the literature. This retrospective analysis shows that genomic assays are a paramount tool in distinguishing between high grade prostatic adenocarcinoma and more aggressive NEPCs.

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