Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer

Carmela Martini¹, Jessica M Logan², Alexandra Sorvina², Colin Gordon², Andrew R Beck², Ben S-Y Ung², Maria C Caruso², Courtney Moore², Ashleigh Hocking³, Ian R D Johnson², Ka Lok Li², Litsa Karageorgos², Ashley M Hopkins⁴, Adrian J Esterman², Chelsea Huzzell², Robert D Brooks², Joanna Lazniewska², Shane M Hickey², Christie Bader², Emma Parkinson-Lawrence², Roberto Weigert⁵, Michael J Sorich⁴, Prerna Tewari⁶, Cara Martin⁶, Sharon O'Toole⁶, Mark Bates⁶, Mark Ward⁶, Bashir Mohammed⁶, Helen Keegan⁶, William Watson⁷, Sophie Prendergast⁸, Sheena Heffernan⁸, Sarah NiMhaolcatha⁸, Roisin O'Connor⁸, Victoria Malone⁸, Marguerite Carter⁸, Katie Ryan⁸, Nathan Brady⁸, Andres Clarke⁸, Filip Sokol⁸, Sarita Prabhakaran⁹, Jürgen Stahl¹⁰, Sonja Klebe¹¹, Hemamali Samaratunga¹², Brett Delahunt¹³, Stavros Selemidis¹⁴, Kim L Moretti¹⁵, Lisa M Butler¹⁶, John J O'Leary⁶, Douglas A Brooks²

Affiliations

¹ Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia. Electronic address: carmela.martino@unisa.edu.au.
² Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia.
³ Department of Anatomical Pathology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
⁴ College of Medicine and Public Health, Flinders University, Flinders Drive, Bedford Park, Adelaide, SA, Australia.
⁵ Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
⁶ Department of Histopathology, Trinity College Dublin, Dublin, Ireland.
⁷ University College Dublin, School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland.
⁸ Department of Pathology, The Coombe Women and Infants University Hospital, Dublin, Ireland.
⁹ Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia; Department of Anatomical Pathology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
¹⁰ Department of Cytopathology and Histopathology, Clinpath Pathology, Adelaide, SA, Australia.
¹¹ Department of Anatomical Pathology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia; Department of Surgical Pathology, SA Pathology at Flinders Medical Centre, Adelaide, SA, Australia.
¹² Aquesta Uropathology and the University of Queensland, Brisbane, Qld, Australia.
¹³ Department of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand.
¹⁴ School of Health and Biomedical Sciences, STEM College, RMIT University, Bundoora, Melbourne, Vic, Australia.
¹⁵ Discipline of Surgery, University of Adelaide, Adelaide, SA, Australia; University of South Australia, Adelaide, SA, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Vic, Australia.
¹⁶ South Australian ImmunoGENomics Cancer Institute and Freemasons Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, SA, Australia; Solid Tumour Program, Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia.

PMID: 36089417
DOI: 10.1016/j.pathol.2022.08.001

Free article

Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer

Carmela Martini et al. Pathology. 2023 Feb.

Free article

. 2023 Feb;55(1):40-51.

doi: 10.1016/j.pathol.2022.08.001. Epub 2022 Aug 20.

Authors

Affiliations

¹ Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia. Electronic address: carmela.martino@unisa.edu.au.
² Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia.
³ Department of Anatomical Pathology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
⁴ College of Medicine and Public Health, Flinders University, Flinders Drive, Bedford Park, Adelaide, SA, Australia.
⁵ Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
⁶ Department of Histopathology, Trinity College Dublin, Dublin, Ireland.
⁷ University College Dublin, School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland.
⁸ Department of Pathology, The Coombe Women and Infants University Hospital, Dublin, Ireland.
⁹ Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia; Department of Anatomical Pathology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
¹⁰ Department of Cytopathology and Histopathology, Clinpath Pathology, Adelaide, SA, Australia.
¹¹ Department of Anatomical Pathology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia; Department of Surgical Pathology, SA Pathology at Flinders Medical Centre, Adelaide, SA, Australia.
¹² Aquesta Uropathology and the University of Queensland, Brisbane, Qld, Australia.
¹³ Department of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand.
¹⁴ School of Health and Biomedical Sciences, STEM College, RMIT University, Bundoora, Melbourne, Vic, Australia.
¹⁵ Discipline of Surgery, University of Adelaide, Adelaide, SA, Australia; University of South Australia, Adelaide, SA, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Vic, Australia.
¹⁶ South Australian ImmunoGENomics Cancer Institute and Freemasons Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, SA, Australia; Solid Tumour Program, Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia.

PMID: 36089417
DOI: 10.1016/j.pathol.2022.08.001

Abstract

Diagnosis and assessment of patients with prostate cancer is dependent on accurate interpretation and grading of histopathology. However, morphology does not necessarily reflect the complex biological changes occurring in prostate cancer disease progression, and current biomarkers have demonstrated limited clinical utility in patient assessment. This study aimed to develop biomarkers that accurately define prostate cancer biology by distinguishing specific pathological features that enable reliable interpretation of pathology for accurate Gleason grading of patients. Online gene expression databases were interrogated and a pathogenic pathway for prostate cancer was identified. The protein expression of key genes in the pathway, including adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif 1 (Appl1), Sortilin and Syndecan-1, was examined by immunohistochemistry (IHC) in a pilot study of 29 patients with prostate cancer, using monoclonal antibodies designed against unique epitopes. Appl1, Sortilin, and Syndecan-1 expression was first assessed in a tissue microarray cohort of 112 patient samples, demonstrating that the monoclonal antibodies clearly illustrate gland morphologies. To determine the impact of a novel IHC-assisted interpretation (the utility of Appl1, Sortilin, and Syndecan-1 labelling as a panel) of Gleason grading, versus standard haematoxylin and eosin (H&E) Gleason grade assignment, a radical prostatectomy sample cohort comprising 114 patients was assessed. In comparison to H&E, the utility of the biomarker panel reduced subjectivity in interpretation of prostate cancer tissue morphology and improved the reliability of pathology assessment, resulting in Gleason grade redistribution for 41% of patient samples. Importantly, for equivocal IHC-assisted labelling and H&E staining results, the cancer morphology interpretation could be more accurately applied upon re-review of the H&E tissue sections. This study addresses a key issue in the field of prostate cancer pathology by presenting a novel combination of three biomarkers and has the potential to transform clinical pathology practice by standardising the interpretation of the tissue morphology.

Keywords: Appl1; Prostate cancer pathology; Sortilin; Syndecan-1; endosome biogenesis.

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Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer

Affiliations

Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer

Authors

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Abstract

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LinkOut - more resources

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Medical

Molecular Biology Databases