The Movember Global Action Plan 1 (GAP1): Unique Prostate Cancer Tissue Microarray Resource

Abstract

Background: The need to better understand the molecular underpinnings of the heterogeneous outcomes of patients with prostate cancer is a pressing global problem and a key research priority for Movember. To address this, the Movember Global Action Plan 1 Unique tissue microarray (GAP1-UTMA) project constructed a set of unique and richly annotated tissue microarrays (TMA) from prostate cancer samples obtained from multiple institutions across several global locations.

Methods: Three separate TMA sets were built that differ by purpose and disease state.

Results: The intended use of TMA1 (Primary Matched LN) is to validate biomarkers that help determine which clinically localized prostate cancers with associated lymph node metastasis have a high risk of progression to lethal castration-resistant metastatic disease, and to compare molecular properties of high-risk index lesions within the prostate to regional lymph node metastases resected at the time of prostatectomy. TMA2 (Pre vs. Post ADT) was designed to address questions regarding risk of castration-resistant prostate cancer (CRPC) and response to suppression of the androgen receptor/androgen axis, and characterization of the castration-resistant phenotype. TMA3 (CRPC Met Heterogeneity)'s intended use is to assess the heterogeneity of molecular markers across different anatomic sites in lethal prostate cancer metastases.

Conclusions: The GAP1-UTMA project has succeeded in combining a large set of tissue specimens from 501 patients with prostate cancer with rich clinical annotation.

Impact: This resource is now available to the prostate cancer community as a tool for biomarker validation to address important unanswered clinical questions around disease progression and response to treatment.

Figure 1.

Representative low-power view of staining of TMA cores from Test TMA1 (Primary Matched LN). Each row shows staining from a single adjacent TMA core chosen from either a primary tumor or lymph node metastatic site from the indicated institutions.

Figure 2.

Representative images of histologic stainings from Test TMA2 (Pre vs. Post ADT) and TMA3 (CRPC Met Heterogeneity). Low-power images from (A) Test TMA2 (Pre vs. Post ADT) and (B) Test TMA 3 (CRPC Met Heterogeneity). Each row shows staining from a single adjacent TMA core from the indicated institutions.