학술논문
Genotype-to-Phenotype Associations in the Aggressive Variant Prostate Cancer Molecular Profile (AVPC-m) Components.
Document Type
Academic Journal
Author
Soundararajan R; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Viscuse P; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Pilie P; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Liu J; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.; Logotheti S; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Laberiano Fernández C; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Lorenzini D; Department of Pathology and Laboratory Medicine, Fondazione IRCCS Instituto Nazionale dei Tumori, 20133 Milan, Italy.; Hoang A; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Lu W; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Soto LMS; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Wistuba II; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Xu M; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.; Song X; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.; Shepherd PDA; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Navone NM; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Tidwell RSS; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA.; Lozano G; Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Logothetis C; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Zhang J; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.; Long JP; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA.; Estecio MR; Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Tzelepi V; Department of Pathology, University of Patras, 26504 Patras, Greece.; Aparicio AM; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101526829 Publication Model: Electronic Cited Medium: Print ISSN: 2072-6694 (Print) Linking ISSN: 20726694 NLM ISO Abbreviation: Cancers (Basel) Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2072-6694
Abstract
The aggressive variant prostate cancer molecular profile (AVPC-m), composed of combined defects in TP53, RB1 and PTEN, characterizes a subset of prostate cancers linked to androgen indifference and platinum sensitivity. To contribute to the optimization of the AVPC-m assessment for inclusion in prospective clinical trials, we investigated the status of the AVPC-m components in 28 patient tumor-derived xenografts (PDXs) developed at MDACC. We subjected single formalin-fixed, paraffin-embedded (FFPE) blocks from each PDX to immunohistochemistry (IHC), targeted next-generation genomic sequencing (NGS) and Clariom-S Affymetrix human microarray expression profiling. Standard validated IHC assays and a 10% labeling index cutoff resulted in high reproducibility across three separate laboratories and three independent readers for all tumor suppressors, as well as strong correlations with loss-of-function transcriptional scores (LOF-TS). Adding intensity assessment to labeling indices strengthened the association between IHC results and LOF-TS for TP53 and RB1, but not for PTEN. For TP53, genomic alterations determined by NGS had slightly higher agreement scores with LOF-TS than aberrant IHC, while for RB1 and PTEN, NGS and IHC determinations resulted in similar agreement scores with LOF-TS. Nonetheless, our results indicate that the AVPC-m components can be assessed reproducibly by IHC using various widely available standardized assays.