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. 2023 May;83(7):641-648.
doi: 10.1002/pros.24497. Epub 2023 Feb 13.

Clinical, pathologic, and molecular features of amphicrine prostate cancer

Laura S Graham  1 , Michael C Haffner  2 , Erolcan Sayar  2 , Agnes Gawne  2 , Michael T Schweizer  3   4 , Colin C Pritchard  5 , Ilsa Coleman  2 , Peter S Nelson  2   3 , Evan Y Yu  3   4
Affiliations

Clinical, pathologic, and molecular features of amphicrine prostate cancer

Laura S Graham et al. Prostate. 2023 May.

Abstract

Background: Amphicrine prostate carcinoma (AMPC) is a poorly defined subset of prostate cancer in which cells co-express luminal prostate epithelial and neuroendocrine markers. The optimal treatment strategy is unknown. We sought to further characterize the clinical, histomorphologic, and molecular characteristics of AMPC and to identify areas of potential future treatment investigations.

Methods: We retrospectively identified 17 cases of AMPC at a single institution, defined as synaptophysin expression in >70% of cells and co-expression of androgen receptor (AR) signaling markers (either AR, PSA, or NKX3.1) in >50% of cells. Clinical and histologic features of AMPC cases as well as response to treatment and clinical outcomes were described.

Results: Five AMPC cases arose de novo in the absence of prior systemic treatment and behaved distinctly from cases that were treatment-emergent. In these de novo cases, despite expression of neuroendocrine markers, prognosis appeared more favorable than high-grade neuroendocrine carcinoma, with two (40%) patients with de novo metastatic disease, universal response to androgen deprivation therapy, and no deaths at a median follow-up of 12.3 months. Treatment-emergent AMPC arose a median of 41.1 months after androgen deprivation therapy initiation and was associated with poor response to therapy.

Conclusions: We show that amphicrine prostate cancer is a unique entity and differs in clinical and molecular features from high-grade neuroendocrine carcinomas of the prostate. Our study highlights the need to recognize AMPC as a unique molecularly defined subgroup of prostate cancer.

Keywords: amphicrine prostate cancer; castration resistant prostate cancer; neuroendocrine; synaptophysin.

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Conflict of interest statement

Disclosure/Conflict of Interest Statement: MTS: Paid consultant and/or received Honoria from Sanofi, AstraZeneca, PharmaIn and Resverlogix. He has received research funding to his institution from Zenith Epigenetics, Bristol Myers Squibb, Merck, Immunomedics, Janssen, AstraZeneca, Pfizer, Madison Vaccines, Hoffman-La Roche, Tmunity, SignalOne Bio and Ambrx, Inc. EY: Consulting (personal) – Advanced Accelerator Applications, Bayer, Clovis, Exelixis, Janssen, Oncternal, Merck. Grant funding (to institution) – Bayer, Blue Earth, Daiichi-Sankyo, Dendreon, Lantheus, Merck, Seagen, Taiho

Figures

Figure 1.
Figure 1.
Histomorphological and immunophenotypic characterization of amphicrine prostate cancers. Representative micrographs show H&E, synaptophysin (SYP) and NKX3.1 immunohistochemistry. Note the diffuse positivity for SYP and NKX3.1 in all cases. Scale bars denote 20 um.
Figure 2.
Figure 2.
Treatment and clinical outcomes of men with AMPC. A. Swimmers plot showing treatment before and after amphicrine diagnosis (noted as *). B. Overall survival from time of amphicrine diagnosis. Red= Treatment-Emergent AMPC, blue = de novo AMPC.
Figure 3.
Figure 3.
A. Disease specific (DS) survival of AR+/NE- and AR+/NE+ (amphicrine) tumors in The Cancer Genome Atlas (TCGA) dataset. B. Progression free (PF) survival of AR+/NE- and AR+/NE+ (amphicrine) tumors in the TCGA dataset.
Figure 4.
Figure 4.
A. Overall survival in SU2C/PCF cohort with four molecularly defined subsets of prostate cancer. B. Gene expression heatmap of tumor specimens from the University of Washington rapid autopsy program.
See this image and copyright information in PMC

References

    1. Graham L, Schweizer MT: Targeting persistent androgen receptor signaling in castration-resistant prostate cancer. Med Oncol 33:44, 2016 - PubMed
    1. Aggarwal R, Huang J, Alumkal JJ, et al. : Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study. J Clin Oncol 36:2492–2503, 2018 - PMC - PubMed
    1. Yamada Y, Beltran H: Clinical and Biological Features of Neuroendocrine Prostate Cancer. Curr Oncol Rep 23:15, 2021 - PMC - PubMed
    1. Labrecque MP, Coleman IM, Brown LG, et al. : Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer. J Clin Invest 130:4492–4505, 2019 - PMC - PubMed
    1. Bluemn EG, Coleman IM, Lucas JM, et al. : Androgen Receptor Pathway- Independent Prostate Cancer Is Sustained through FGF Signaling. Cancer Cell 32:474–489 e6, 2017 - PMC - PubMed

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