Framework for the pathology workup of metastatic castration-resistant prostate cancer biopsies Journal Article


Authors: Haffner, M. C.; Morris, M. J.; Ding, C. K. C.; Sayar, E.; Mehra, R.; Robinson, B.; True, L. D.; Gleave, M.; Lotan, T. L.; Aggarwal, R.; Huang, J.; Loda, M.; Nelson, P. S.; Rubin, M. A.; Beltran, H.
Article Title: Framework for the pathology workup of metastatic castration-resistant prostate cancer biopsies
Abstract: Lineage plasticity and histologic transformation from prostate adenocarcinoma to neuroendocrine (NE) prostate cancer (NEPC) occur in up to 15% to 20% of patients with castration-resistant prostate cancer (CRPC) as a mechanism of treatment resistance and are associated with aggressive disease and poor prognosis. NEPC tumors typically display small cell carcinoma morphology with loss of androgen receptor (AR) expression and gain of NE lineage markers. However, there is a spectrum of phenotypes that are observed during the lineage plasticity process, and the clinical significance of mixed histologies or those that co-express AR and NE markers or lack all markers is not well defined. Translational research studies investigating NEPC have used variable definitions, making clinical trial design challenging. In this manuscript, we discuss the diagnostic workup of metastatic biopsies to help guide the reproducible classification of phenotypic CRPC subtypes. We recommend classifying CRPC tumors based on histomorphology (adenocarcinoma, small cell carcinoma, poorly differentiated carcinoma, other morphologic variant, or mixed morphology) and IHC markers with a priority for AR, NK3 homeobox 1, insulinoma-associated protein 1, synaptophysin, and cell proliferation based on Ki-67 positivity, with additional markers to be considered based on the clinical context. Ultimately, a unified workup of metastatic CRPC biopsies can improve clinical trial design and eventually practice. ©2024 American Association for Cancer Research.
Keywords: immunohistochemistry; human tissue; adenocarcinoma; ki 67 antigen; cell proliferation; metabolism; metastasis; basal cell carcinoma; transcription factor; tumor biopsy; cell differentiation; pathology; tumor marker; biopsy; prostate specific membrane antigen; fluorescence in situ hybridization; diagnosis; neoplasm metastasis; androgen receptor; prostate adenocarcinoma; receptors, androgen; neuroendocrine carcinoma; carcinoma, neuroendocrine; insulinoma; synaptophysin; castration resistant prostate cancer; high throughput sequencing; humans; human; male; article; prostatic neoplasms, castration-resistant; metastatic castration resistant prostate cancer; biomarkers, tumor
Journal Title: Clinical Cancer Research
Volume: 31
Issue: 3
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2025-02-01
Start Page: 466
End Page: 478
Language: English
DOI: 10.1158/1078-0432.Ccr-24-2061
PUBMED: 39589343
PROVIDER: scopus
PMCID: PMC11790385
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Michael Morris
    583 Morris