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Molecular subtypes of metastatic prostate cancer: from pathophysiology to diagnosis.

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Histopathology 📖 저널 OA 39.5% 2021: 0/1 OA 2022: 1/1 OA 2023: 0/1 OA 2024: 0/2 OA 2025: 5/8 OA 2026: 25/61 OA 2021~2026 2026 Vol.88(1) p. 24-39
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Dsouza JM, Sayar E, Schweizer MT, Harmon S, Morrissey C, Beltran H, Nelson PS, Cheng L, Ding CC, Haffner MC

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Metastatic prostate cancer (mPC) is characterized by molecular and phenotypic heterogeneity.

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APA Dsouza JM, Sayar E, et al. (2026). Molecular subtypes of metastatic prostate cancer: from pathophysiology to diagnosis.. Histopathology, 88(1), 24-39. https://doi.org/10.1111/his.70033
MLA Dsouza JM, et al.. "Molecular subtypes of metastatic prostate cancer: from pathophysiology to diagnosis.." Histopathology, vol. 88, no. 1, 2026, pp. 24-39.
PMID 41384688 ↗
DOI 10.1111/his.70033

Abstract

Metastatic prostate cancer (mPC) is characterized by molecular and phenotypic heterogeneity. With increasing guideline-driven use of metastatic biopsies, more mPC specimens are being evaluated in surgical pathology. However, unlike localized prostate cancer, no standardized framework currently exists to guide the diagnostic workup of metastatic biopsies or reliably determine phenotypic subtypes. While many mPCs retain conventional acinar features, a growing subset exhibits phenotypic plasticity - including loss of prostate epithelial identity and emergence of neuroendocrine or other divergent lineages. This phenotypic diversity often occurs in castration-resistant prostate cancer as a mechanism of resistance to chronic androgen receptor pathway inhibition and is characterized by genomic alterations and epigenetic reprogramming. This review outlines the histologic and molecular spectrum of mPC and proposes a practical, pathology-informed diagnostic approach integrating morphologic assessment and immunohistochemistry. Adoption of a standardized diagnostic framework and multidisciplinary integration will be useful for employing precision oncology in advanced mPC.

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