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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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Framework for the Pathology Workup of Metastatic Castration-Resistant Prostate Cancer Biopsies.

Michael C Haffner1,2,3, Michael J Morris4, Chien-Kuang C Ding5

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Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
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Summary

Neuroendocrine prostate cancer (NEPC) arises from prostate adenocarcinoma in some castration-resistant cases, often indicating aggressive disease. Standardized diagnostic criteria for classifying these challenging subtypes are proposed to improve research and treatment.

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Area of Science:

  • Oncology
  • Pathology
  • Translational Research

Background:

  • Prostate adenocarcinoma can transform into neuroendocrine prostate cancer (NEPC) in up to 20% of castration-resistant cases, a process linked to treatment resistance, aggressive disease, and poor prognosis.
  • NEPC typically shows small cell morphology, loss of androgen receptor (AR) expression, and gain of neuroendocrine (NE) markers, but a spectrum of phenotypes exists, complicating diagnosis and clinical trial design.
  • The clinical significance of mixed histologies or variable marker expression in phenotypic CRPC subtypes remains poorly defined.

Purpose of the Study:

  • To discuss the diagnostic workup of metastatic biopsies for reproducible classification of phenotypic castration-resistant prostate cancer (CRPC) subtypes.
  • To propose a unified approach for classifying CRPC tumors based on histomorphology and immunohistochemistry (IHC) markers.

Main Methods:

  • Review and discussion of diagnostic criteria for metastatic CRPC biopsies.
  • Recommendation for classification based on histomorphology (adenocarcinoma, small cell carcinoma, poorly differentiated carcinoma, mixed morphology, etc.).
  • Prioritization of IHC markers including AR, NK3 homeobox 1, insulinoma-associated protein 1, synaptophysin, and Ki-67, with consideration for additional markers based on clinical context.

Main Results:

  • A spectrum of CRPC phenotypes exists beyond typical NEPC, including mixed histologies and variable AR/NE marker expression.
  • Current variable definitions for NEPC hinder translational research and clinical trial design.
  • Proposed classification framework based on histomorphology and a prioritized panel of IHC markers.

Conclusions:

  • A standardized diagnostic workup for metastatic CRPC biopsies is crucial for reproducible classification of phenotypic subtypes.
  • Implementing the recommended classification approach can improve clinical trial design and patient care.
  • Unified classification will facilitate better understanding and management of treatment-resistant prostate cancer.