Supplementary Figure 4 from Framework for the Pathology Workup of Metastatic Castration-Resistant Prostate Cancer Biopsies

Haffner, Michael C.; Morris, Michael J.; Ding, Chien-Kuang C.; Sayar, Erolcan; Mehra, Rohit; Robinson, Brian; True, Lawrence D.; Gleave, Martin; Lotan, Tamara L.; Aggarwal, Rahul; Huang, Jiaoti; Loda, Massimo; Nelson, Peter S.; Rubin, Mark A.; Beltran, Himisha

doi:10.1158/1078-0432.28333040

Supplementary Figure 4 from Framework for the Pathology Workup of Metastatic Castration-Resistant Prostate Cancer Biopsies

journal contribution

posted on 2025-02-03, 08:23 authored by Michael C. Haffner, Michael J. Morris, Chien-Kuang C. Ding, Erolcan Sayar, Rohit Mehra, Brian Robinson, Lawrence D. True, Martin Gleave, Tamara L. Lotan, Rahul Aggarwal, Jiaoti Huang, Massimo Loda, Peter S. Nelson, Mark A. Rubin, Himisha Beltran

Supplementary Figure 4. Example case 4.

Funding

Prostate Cancer Foundation (PCF)

National Cancer Institute (NCI)

United States Department of Health and Human Services

Find out more...

U.S. Department of Defense (DOD)

Doris Duke Charitable Foundation (DDCF)

the V Foundation

Brotman Baty Institute for Precision Medicine

UW/FHCC Institute for Prostate Cancer Research

History

ARTICLE 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.