Immunohistochemical biomarker validation in highly selective needle biopsy microarrays derived from mpMRI‐characterized prostates

Olivier, Jonathan; Stavrinides, Vasilis; Kay, Jonathan; Freeman, Alex; Pye, Hayley; Ahmed, Zeba; Echeverría, Lina María Carmona; Heavey, Susan; Simmons, Lucy A. M.; Kanthabalan, Abi; Arya, Manit; Briggs, T.; Barratt, Dean C.; Charman, Susan C.; Gelister, J. S. K.; Hawkes, David J.; Hu, Yipeng; Jameson, Charles; McCartan, Neil; Punwani, Shonit; Muelen, Jan van der; Moore, Caroline M.; Emberton, Mark; Ahmed, Hashim U.; Whitaker, Hayley C.

doi:10.1002/pros.23698

Cited by 10 publications

(8 citation statements)

References 21 publications

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“…We observe that PSAD change prompts further assessments through imaging or biopsy and is, therefore, associated with outcome. Future research should expand on these considerations and explore the potential of multivariable models with additional longitudinal predictors beyond PSAD [9,10]. There was a steady increase in mean prostate volume over time (spline curve shown), at an approximate average rate of 3.3 mL/ year.…”

Section: Discussionmentioning

confidence: 99%

Mapping PSA density to outcome of MRI-based active surveillance for prostate cancer through joint longitudinal-survival models

Stavrinides

Παπαγεωργίου

Danks

et al. 2021

Prostate Cancer Prostatic Dis

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Section: Discussionmentioning

confidence: 99%

Mapping PSA density to outcome of MRI-based active surveillance for prostate cancer through joint longitudinal-survival models

Stavrinides

Παπαγεωργίου

Danks

et al. 2021

Prostate Cancer Prostatic Dis

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“…The STAR proteins are splicing factors with well characterised roles in spermatogenesis, adipogenesis, neuronal development and tumourigenesis [30,32,33,34]. Using immunohistochemistry we established the over expression of T-STAR in prostate tumourigenesis showing that nuclear T-STAR expression was low in benign tissue and upregulated in tumour tissue based on a two-tailed Mann–Whitney test ( p < 0.0001) [35] (Figure 2B,C). Interestingly, T-STAR expression also associated with Likert score, an ordinal score (ranging from 1–5) that denotes the likelihood of a significant tumour on magnetic resonance imaging (MRI, Figure 2C), but was not significantly associated with Gleason Grade despite a trend towards higher expression with increasing Gleason Grade ( p = 0.15).…”

Section: Resultsmentioning

confidence: 99%

“…Tissue microarrays constructed from needle biopsies collected from the PICTURE trial consisted of paired tissue from 249 men as previous described [35]. Slides were scanned using a NanoZoomer-SQ digital slide scanner (Hamamatsy Photonics, Japan) and each individual core was assessed for the presence of cancer by a trained uro-pathologist (AF) as well as being scored by two independent scorers (HW and VS) without prior knowledge to clinical data.…”

Section: Methodsmentioning

confidence: 99%

The Oncogene Metadherin Interacts with the Known Splicing Proteins YTHDC1, Sam68 and T-STAR and Plays a Novel Role in Alternative mRNA Splicing

Luxton

Simpson

Mills

et al. 2019

Cancers

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Oncogenic metadherin is a key contributor to tumourigenesis with metadherin expression and cytoplasmic localisation previously linked to poor survival. A number of reports have shown metadherin localises specifically to nuclear speckles known to be rich in RNA-binding proteins including the splicing proteins YTHDC1, Sam68 and T-STAR, that have been shown to select alternative splice sites in mRNA of tumour-associated proteins including BRCA, MDM2 and VEGF. Here we investigate the interaction and relationship between metadherin and the splice factors YTHDC1, T-STAR and Sam68. Using a yeast two-hybrid assay and immunoprecipitation we show that metadherin interacts with YTHDC1, Sam68 and T-STAR and demonstrate that T-STAR is significantly overexpressed in prostate cancer tissue compared to benign prostate tissue. We also demonstrate that metadherin influences splice site selection in a dose-dependent manner in CD44v5-luc minigene reporter assays. Finally, we demonstrate that prostate cancer patients with higher metadherin expression have greater expression of the CD44v5 exon. CD44v5 expression could be used to discriminate patients with poor outcomes following radical prostatectomy. In this work we show for the first time that metadherin interacts with, and modulates, the function of key components of splicing associated with cancer development and progression.

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“…Multiparametric MRI (mpMRI) has been used to characterize tissue microarrays (TMAs) of prostate needle biopsies with PSA, PSMA, AMACR, p63, MSMB, and other prostatespecific IHC markers. 30 The expression of these markers was described with H-scores that were correlated with the MRI Likert score in malignant and benign tissues; Likert scores of 1 to 5 were used to characterize abnormalities (1 not suspect; 2 hardly suspect; 3 ambiguous; 4 suspect; and 5 highly suspect) to show that there was a statistically significant difference in H-scores between malignant and benign tissues that were independent of the Likert score. There were also no associations between the H-scores with either Gleason grade or Likert scores within each of the benign or malignant groups.…”

Section: Markers Of Genitourinary Tumorsmentioning

confidence: 99%

Overview of established and emerging immunohistochemical biomarkers and their role in correlative studies in MRI

Alvi

Gupta

Borok

et al. 2019

Magnetic Resonance Imaging

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Clinical practice in radiology and pathology requires professional expertise and many years of training to visually evaluate and interpret abnormal phenotypic features in medical images and tissue sections to generate diagnoses that guide patient management and treatment. Recent advances in digital image analysis methods and machine learning have led to significant interest in extracting additional information from medical and digital whole‐slide images in radiology and pathology, respectively. This has led to significant interest and research in radiomics and pathomics to correlate phenotypic features of disease with image analytics in order to identify image‐based biomarkers. The expanding role of big data in radiology and pathology parallels the development and role of immunohistochemistry (IHC) in the daily practice of pathology. IHC methods were initially developed to provide additional information to help classify tumors and then transformed into an indispensable tool to guide treatment in many types of cancer. IHC markers are used in daily practice to identify specific types of cells and highlight their distributions in tissues in order to distinguish benign from neoplastic cells, determine tumor origin, subclassify neoplasms, and support and confirm diagnoses. In this regard, radiomics, pathomics, and IHC methods are very similar since they enable the extraction of image‐based features to characterize various properties of diseases. Due to the dramatic advancements in recent radiomics research, we provide a brief overview of the role of established and emerging IHC biomarkers in various tumor types that have been correlated with radiologic biomarkers to improve diagnostic accuracy, predict prognosis, guide patient management, and select treatment strategies. Level of Evidence: 5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:341–354.

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Immunohistochemical biomarker validation in highly selective needle biopsy microarrays derived from mpMRI‐characterized prostates

Cited by 10 publications

References 21 publications

Mapping PSA density to outcome of MRI-based active surveillance for prostate cancer through joint longitudinal-survival models

Mapping PSA density to outcome of MRI-based active surveillance for prostate cancer through joint longitudinal-survival models

The Oncogene Metadherin Interacts with the Known Splicing Proteins YTHDC1, Sam68 and T-STAR and Plays a Novel Role in Alternative mRNA Splicing

Overview of established and emerging immunohistochemical biomarkers and their role in correlative studies in MRI

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