Genotype-to-Phenotype Associations in the Aggressive Variant Prostate Cancer Molecular Profile (AVPC-m) Components
Rama Soundararajan1, Paul Viscuse2, Patrick Pilie2
1Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancers
|July 9, 2022
Summary
Immunohistochemistry (IHC) reliably detects aggressive variant prostate cancer (AVPC-m) molecular profiles, crucial for clinical trials. This method accurately assesses TP53, RB1, and PTEN defects, aiding treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Aggressive variant prostate cancer molecular profile (AVPC-m) involves TP53, RB1, and PTEN defects.
- AVPC-m is associated with androgen indifference and platinum sensitivity.
- Optimizing AVPC-m assessment is vital for clinical trial integration.
Purpose of the Study:
- To investigate the reproducibility of assessing AVPC-m components (TP53, RB1, PTEN) in patient tumor-derived xenografts (PDXs).
- To evaluate immunohistochemistry (IHC) and next-generation sequencing (NGS) for AVPC-m component detection.
- To correlate molecular profiling results with loss-of-function transcriptional scores (LOF-TS).
Main Methods:
- Utilized 28 patient tumor-derived xenografts (PDXs).
- Performed immunohistochemistry (IHC), targeted next-generation genomic sequencing (NGS), and microarray expression profiling on FFPE tissues.
- Assessed reproducibility across three laboratories and three readers using a 10% labeling index cutoff.
Main Results:
- Standard IHC assays demonstrated high reproducibility for TP53, RB1, and PTEN, correlating well with LOF-TS.
- Intensity assessment enhanced IHC-LOF-TS association for TP53 and RB1.
- NGS showed slightly higher agreement with LOF-TS for TP53 compared to IHC, while RB1 and PTEN showed similar agreement between methods.
Conclusions:
- Immunohistochemistry (IHC) is a reproducible method for assessing AVPC-m components.
- Standardized IHC assays are suitable for AVPC-m assessment in prospective clinical trials.
- Both IHC and NGS are valuable tools for evaluating AVPC-m, with IHC offering a reproducible and accessible option.
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