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1. Reinterpretation of prostate cancer pathology by Appl1, Sortilin and Syndecan-1 biomarkers

Author

Logan, Jessica M., Martini, Carmela, Sorvina, Alexandra, Johnson, Ian R. D., Brooks, Robert D., Caruso, Maria C., Huzzell, Chelsea, Moore, Courtney R., Karageorgos, Litsa, Butler, Lisa M., Tewari, Prerna, Prabhakaran, Sarita, Hickey, Shane M., Klebe, Sonja, Samaratunga, Hemamali, Delahunt, Brett, Moretti, Kim, O’Leary, John J., Brooks, Douglas A., and Ung, Ben S.-Y.

Published
2024
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2. Molecular Characterization of Testicular Mesothelioma and the Role of Asbestos as a Causative Factor

Author

Hocking, Ashleigh Jean, Thomas, Elaine May, Prabhakaran, Sarita, Jolley, Alexandra, Woods, Susan Lesley, Soeberg, Matthew J., and Klebe, Sonja

Subjects
Ventana Medical Systems Inc., Genomics, Tumor proteins, Medical test kit industry, Genomes, Medical equipment and supplies industry, Mesothelioma, Asbestos, Health
Abstract

* Context.--Mesothelioma of the tunica vaginalis testis (TVT) is an extremely rare form of mesothelioma. Objective.--To compare the clinical and molecular characteristics of mesothelioma of the TVT with those of mesothelioma at other more common sites, including the relationship with exposure to asbestos. Design.--We present clinical and pathological data for 9 cases of primary TVT mesothelioma. We performed whole-genome sequencing on 3 cases for the first time. Results.--The majority (7 of 9 cases) of TVT mesotheliomas were epithelioid, with the remaining 2 cases showing biphasic morphology. Morphology and immunohistochemical profiles were indistinguishable from mesothelioma elsewhere. Asbestos exposure was documented for 7 of the 9 cases, with no information for 2 cases. The 3 TVT mesothelioma cases that underwent whole-genome sequencing displayed a mutational profile similar to that of mesothelioma at other sites, including NF2 and TP53 mutations. Conclusions.--The clinical and molecular profile of TVT mesothelioma is similar to that of mesothelioma elsewhere. (Arch Pathol Lab Med. 2023;147:1446-1450; doi: 10.5858/arpa.2022-0283-OA), Mesothelioma is a malignancy arising in the mesothelial cells lining serosal surfaces, most frequently occurring in the pleural (>80%) or peritoneal cavities (10%-15%). Exposure to asbestos is recognized as the [...]

Published
2023
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3. Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression

Author

Lazniewska, Joanna, Li, Ka Lok, Johnson, Ian R. D., Sorvina, Alexandra, Logan, Jessica M., Martini, Carmela, Moore, Courtney, Ung, Ben S.-Y., Karageorgos, Litsa, Hickey, Shane M., Prabhakaran, Sarita, Heatlie, Jessica K., Brooks, Robert D., Huzzell, Chelsea, Warnock, Nicholas I., Ward, Mark P., Mohammed, Bashir, Tewari, Prerna, Martin, Cara, O’Toole, Sharon, Edgerton, Laura Bogue, Bates, Mark, Moretti, Paul, Pitson, Stuart M., Selemidis, Stavros, Butler, Lisa M., O’Leary, John J., and Brooks, Douglas A.

Published
2023
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4. Altered endosomal-lysosomal biogenesis in melanoma

Author

Lam, Giang T., Sorvina, Alexandra, Martini, Carmela, Prabhakaran, Sarita, Ung, Ben S.-Y., Lazniewska, Joanna, Moore, Courtney R., Beck, Andrew R., Hopkins, Ashley M., Johnson, Ian R.D., Caruso, Maria C., Hickey, Shane M., Brooks, Robert D., Jackett, Louise, Karageorgos, Litsa, Foster-Smith, Erwin J., Malone, Victoria, Klebe, Sonja, O'Leary, John J., Brooks, Douglas A., and Logan, Jessica M.

Published
2023
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6. Insights into Melanoma Clinical Practice: A Perspective for Future Research

Author

Lam, Giang T., primary, Martini, Carmela, additional, Brooks, Tiffany, additional, Prabhakaran, Sarita, additional, Hopkins, Ashley M., additional, Ung, Ben S.-Y., additional, Tang, Jingying, additional, Caruso, Maria C., additional, Brooks, Robert D., additional, Johnson, Ian R. D., additional, Sorvina, Alexandra, additional, Hickey, Shane M., additional, Karageorgos, Litsa, additional, Klebe, Sonja, additional, O’Leary, John J., additional, Brooks, Douglas A., additional, and Logan, Jessica M., additional

Published
2023
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7. Prediction of Prostate Cancer Biochemical and Clinical Recurrence Is Improved by IHC-Assisted Grading Using Appl1, Sortilin and Syndecan-1

Author

Logan, Jessica M., primary, Hopkins, Ashley M., additional, Martini, Carmela, additional, Sorvina, Alexandra, additional, Tewari, Prerna, additional, Prabhakaran, Sarita, additional, Huzzell, Chelsea, additional, Johnson, Ian R. D., additional, Hickey, Shane M., additional, Ung, Ben S.-Y., additional, Lazniewska, Joanna, additional, Brooks, Robert D., additional, Moore, Courtney R., additional, Caruso, Maria C., additional, Karageorgos, Litsa, additional, Martin, Cara M., additional, O’Toole, Sharon, additional, Bogue Edgerton, Laura, additional, Ward, Mark P., additional, Bates, Mark, additional, Selemidis, Stavros, additional, Esterman, Adrian, additional, Heffernan, Sheena, additional, Keegan, Helen, additional, Ní Mhaolcatha, Sarah, additional, O’Connor, Roisin, additional, Malone, Victoria, additional, Carter, Marguerite, additional, Ryan, Katie, additional, Clarke, Andres, additional, Brady, Nathan, additional, Klebe, Sonja, additional, Samaratunga, Hemamali, additional, Delahunt, Brett, additional, Sorich, Michael J., additional, Moretti, Kim, additional, Butler, Lisa M., additional, O’Leary, John J., additional, and Brooks, Douglas A., additional

Published
2023
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12. Progression of Well-Differentiated Papillary Mesothelial Tumour to Mesothelioma in a Patient with Ehlers Danlos Syndrome

Author

Prabhakaran, Sarita, Hussey, Matthew, O'Byrne, Ken, Klebe, Sonja, Prabhakaran, Sarita, Hussey, Matthew, O'Byrne, Ken, and Klebe, Sonja

Abstract

Well-differentiated papillary mesothelioma has been renamed well-differentiated papillary mesothelial tumour (WDPMT) in the current WHO classification because all mesotheliomas are now regarded as malignant. WDPMT is now defined as a non-invasive papillary mesothelial proliferation, with retained labelling for BAP1-desirable. The current WHO classification also includes mesothelioma in situ (MIS), which is defined as pre-invasive flat or papillary proliferation of mesothelial cells with a loss of BAP1 or MTAP. WDPMT has been variably defined in the past but was thought to occur more commonly in women and pursue a more indolent course than mesothelioma, but its progression to invasive disease has occasionally been reported. Here, we report a case of a 68-year-old woman with a history of asbestos exposure and an underlying diagnosis of Ehlers Danlos syndrome who was diagnosed with symptomatic WDPMT of the peritoneum that progressed to mesothelioma within two years. On retrospective analysis, the WDPMT showed a loss of BAP1. We suggest that a loss of BAP1 in WDPMT should be reported, since these lesions may show aggressive behaviour, and that they may best be regarded as similar to mesothelioma in situ. View Full-Text

Published
2021

13. A comparison of diagnostic panels in the immunohistochemical analysis of lung cancer

Author

Prabhakaran,Sarita, Xing,Guang, Hocking,Ashleigh, Hussey,Matthew, Henderson,Douglas W., and Klebe,Sonja

Subjects
Pathology and Laboratory Medicine International
Abstract

Sarita Prabhakaran,1 Guang Xing,1 Ashleigh Hocking,1 Matthew Hussey,2 Douglas W Henderson,1,†Sonja Klebe1,2 1Department of Anatomical Pathology, Flinders University, Bedford Park, SA, Australia; 2Department of Anatomical Pathology, SA Pathology, Flinders Medical Centre, SA, Australia†Professor Douglas Henderson passed away on September 17, 2018Correspondence: Sonja KlebeDepartment of Anatomical Pathology, Flinders Medical Centre and Flinders University, Bedford Park, SA 5042, AustraliaTel +61 088 204 3936Fax +61 88 374 1437Email sonja.klebe@sa.gov.auPurpose: Classification of non-small cell lung carcinoma (NSCLC), as adenocarcinoma or squamous cell carcinoma, is important both in the diagnosis and treatment of lung cancer. Use of appropriate markers for this identification is crucial in order to conserve patient tissue for further molecular testing that could guide treatment decisions and have prognostic implications.Patients and methods: We constructed tissue microarrays from archival resections of 200 NSCLC that were previously subtyped based on morphology and immunohistochemistry (IHC) in some cases. We performed IHC with three TTF-1 clones (SP141, SPT24 and 8G7G3/1), Napsin A, p40, p63 and CK5/6 and panels of four or two markers that best help identify adenocarcinoma and squamous cell carcinoma were ascertained.Results: Our results showed that the best four-marker panel utilized TTF-1 (clone SP141), Napsin A, p63 and CK5/6 with a sensitivity of 98.3% and high specificity of 91.7%. The best two-marker panel was TTF-1 (clone SP141) and p63 with 96.5% sensitivity and 85.71% specificity.Conclusion: As there are variations in the performance of different clones of TTF-1 IHC antibodies, the clone chosen can increase the diagnostic value in differentiating adenocarcinoma from squamous cell carcinoma. In the panels analyzed, the survival of cases concordant with the diagnosis had longer survival compared to those that were discordant. The difference was however not statistically significant (p>0.05).Keywords: non-small cell lung carcinoma, immunohistochemistry, squamous cell carcinoma, adenocarcinoma

Published
2019

14. Prognostic significance of TRAIL death receptors in Middle Eastern colorectal carcinomas and their correlation to oncogenic KRAS alterations

Author

Hussain Azhar R, Al-Dayel Fouad, Alhomoud Samar, Ashari Luai H, Abduljabbar Alaa, Al-Sanea Nasser, George Thara, Qadri Zeeshan, Abubaker Jehad, Prabhakaran Sarita E, Bavi Prashant, Uddin Shahab, and Al-Kuraya Khawla S

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumour necrosis factor cytokine family that induces apoptosis upon binding to its death domain containing receptors, TRAIL receptor 1 (DR4) and TRAIL receptor 2 (DR5). Expression of TRAIL receptors is higher in colorectal carcinoma (CRC) as compared to normal colorectal mucosa and targeted therapy with TRAIL leads to preferential killing of tumor cells sparing normal cells. Methods We investigated the expression of TRAIL and its receptors in a tissue microarray cohort of 448 Middle Eastern CRC. We also studied the correlation between TRAIL receptors and various clinico-pathological features including key molecular alterations and overall survival. Results CRC subset with TRAIL-R1 expression was associated with a less aggressive phenotype characterized by early stage (p = 0.0251) and a histology subtype of adenocarcinomas (p = 0.0355). Similarly CRC subset with TRAIL-R2 expression was associated with a well-differentiated tumors (p < 0.0001), histology subtype of adenocarcinomas (p = 0.0010) and tumors in left colon (p = 0.0009). Over expression of pro apoptotic markers: p27KIP1 and KRAS4A isoforms was significantly higher in CRC subset with TRAIL-R1 and TRAIL-R2 expression; TRAIL-R1 expression was also associated with cleaved caspase-3(p = 0.0011). Interestingly, TRAIL-R2 expression was associated with a microsatellite stable (MS--S/L) phenotype (p = 0.0003) and with absence of KRAS mutations (p = 0.0481). Conclusion TRAIL-R1 expression was an independent prognostic marker for better survival in all CRC samples and even in the CRC group that received adjuvant therapy. The biological effects of TRAIL in CRC models, its enhancement of chemosensitivity towards standard chemotherapeutic agents and the effect of endogenous TRAIL receptor levels on survival make TRAIL an extremely attractive therapeutic target.

Published
2010
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18. ALK alteration is a frequent event in aggressive breast cancers

Author

Siraj, Abdul K., primary, Beg, Shaham, additional, Jehan, Zeenath, additional, Prabhakaran, Sarita, additional, Ahmed, Maqbool, additional, R.Hussain, Azhar, additional, Al-Dayel, Fouad, additional, Tulbah, Asma, additional, Ajarim, Dahish, additional, and Al-Kuraya, Khawla S., additional

Published
2015
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20. A very low incidence of BRAF mutations in Middle Eastern colorectal carcinoma

Author

Siraj, Abdul K, primary, Bu, Rong, additional, Prabhakaran, Sarita, additional, Bavi, Prashant, additional, Beg, Shaham, additional, Al Hazmi, Mohsen, additional, Al-Rasheed, Maha, additional, Alobaisi, Khadija, additional, Al-Dayel, Fouad, additional, AlManea, Hadeel, additional, Al-Sanea, Nasser, additional, Uddin, Shahab, additional, and Al-Kuraya, Khawla S, additional

Published
2014
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22. Abstract 2104: Frequent inactivation of A20 and its prognostic significance in Middle Eastern colorectal carcinoma

Author

Abubaker, Jehad, primary, Bavi, Prashant, additional, Uddin, Shahab, additional, Jehan, Zeenath, additional, Ahmed, Maqbool, additional, Al-Sanea, Nasser, additional, Abduljabbar, Alaa, additional, Ashari, Luai H., additional, Alhomoud, Samar, additional, Al-Dayel, Fouad, additional, Sultana, Mehar, additional, Al-Haqawi, Wael, additional, Al-Rasheed, Maha, additional, Hassan, Nurul, additional, Qadri, Zeeshan, additional, George, Thara, additional, Prabhakaran, Sarita E., additional, Balde, Valorie, additional, Siraj, Abdul K., additional, and Al-Kuraya, Khawla S., additional

Published
2011
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23. Abstract 4412: Prognostic significance of NF-κB in Middle Eastern diffuse large B cell lymphoma and efficacy of NF-κB inhibition as a viable therapeutic target

Author

Bavi, Prashant, primary, Uddin, Shahab, additional, Bu, Rong, additional, Ahmed, Maqbool, additional, Abubaker, Jehad, additional, Al-Dayel, Fouad, additional, Balde, Valorie, additional, Naidu, Padmanabhan, additional, Al-Dossari, Hassan, additional, Qadri, Zeeshan, additional, Prabhakaran, Sarita E., additional, Hussain, Azhar R., additional, and Al-Kuraya, Khawla S., additional

Published
2011
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24. Abstract 2980: Clinico-pathological correlation of UBE2C alterations in colorectal carcinoma and efficacy of UBE2C inhibition by proteosome inhibitor as a viable therapeutic target

Author

Bu, Rong, primary, Bavi, Prashant, additional, Hussain, Azhar R., additional, Jehan, Zeenath, additional, Abubaker, Jehad, additional, Al-Sanea, Nasser A., additional, Abduljabbar, Alaa S., additional, Ashari, Luai H., additional, Al-Homoud, Samar J., additional, Al-Dayel, Fouad, additional, George, Thara, additional, Qadri, Zeeshan, additional, Hassan, Nurul, additional, Prabhakaran, Sarita E., additional, Ahmed, Maqbool, additional, Uddin, Shahab, additional, and Al-Kuraya, Khawla S., additional

Published
2011
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25. Abstract 1069: Clinicopathological significance of CARD10 alterations in Middle Eastern colorectal cancer

Author

Abubaker, Jehad, primary, Bavi, Prashant, additional, Jehan, Zeenath, additional, Ahmed, Maqbool, additional, Al-Haqawi, Wael, additional, Sultana, Mehar, additional, Prabhakaran, Sarita, additional, Al-Sanea, Nasser, additional, Abduljabbar, Alaa, additional, Ashari, Luai H., additional, Alhomoud, Samar, additional, Al-Dayel, Fouad, additional, Uddin, Shahab, additional, and Al-Kuraya, Khawla S., additional

Published
2011
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26. Abstract 2711: JC virus T-Antigen (SV40) is an independent prognostic marker for poor disease free survival in epithelial ovarian carcinoma

Author

Bavi, Prashant, primary, Aubaker, Jehad, additional, Prabhakaran, Sarita E., additional, Sultna, Mehar, additional, Al-Dayel, Fouad, additional, Saravanan, Thangavel, additional, Qadri, Zeeshan, additional, Balde, Valorie, additional, Naidu, Padmanabhan, additional, Al-Dossari, Hassan, additional, Uddin, Shahab, additional, and Al-Kuraya, Khawla, additional

Published
2011
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27. Prognostic significance of TRAIL death receptors in Middle Eastern colorectal carcinomas and their correlation to oncogenic KRAS alterations

Author

Bavi, Prashant, primary, Prabhakaran, Sarita E, additional, Abubaker, Jehad, additional, Qadri, Zeeshan, additional, George, Thara, additional, Al-Sanea, Nasser, additional, Abduljabbar, Alaa, additional, Ashari, Luai H, additional, Alhomoud, Samar, additional, Al-Dayel, Fouad, additional, Hussain, Azhar R, additional, Uddin, Shahab, additional, and Al-Kuraya, Khawla S, additional

Published
2010
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28. Prognostic significance of TRAIL death receptorsin Middle Eastern colorectal carcinomas and theircorrelation to oncogenic KRAS alterations.

Author

Bavi, Prashant, Prabhakaran, Sarita E., Abubaker, Jehad, Qadri, Zeeshan, George, Thara, Al-Sanea, Nasser, Abduljabbar, Alaa, Ashari, Luai H., Alhomoud, Samar, Al-Dayel, Fouad, Hussain, Azhar R., Uddin, Shahab, and Al-Kuraya, Khawla S.

Subjects
*COLON cancer, *TUMOR necrosis factors, *APOPTOSIS, *CYTOKINES, *MUCOUS membranes
Abstract

Background: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumour necrosis factor cytokine family that induces apoptosis upon binding to its death domain containing receptors, TRAIL receptor 1 (DR4) and TRAIL receptor 2 (DR5). Expression of TRAIL receptors is higher in colorectal carcinoma (CRC) as compared to normal colorectal mucosa and targeted therapy with TRAIL leads to preferential killing of tumor cells sparing normal cells. Methods: We investigated the expression of TRAIL and its receptors in a tissue microarray cohort of 448 Middle Eastern CRC. We also studied the correlation between TRAIL receptors and various clinico-pathological features including key molecular alterations and overall survival. Results: CRC subset with TRAIL-R1 expression was associated with a less aggressive phenotype characterized by early stage (p = 0.0251) and a histology subtype of adenocarcinomas (p = 0.0355). Similarly CRC subset with TRAILR2 expression was associated with a well-differentiated tumors (p < 0.0001), histology subtype of adenocarcinomas (p = 0.0010) and tumors in left colon (p = 0.0009). Over expression of pro apoptotic markers: p27KIP1 and KRAS4A isoforms was significantly higher in CRC subset with TRAIL-R1 and TRAIL-R2 expression; TRAIL-R1 expression was also associated with cleaved caspase-3(p = 0.0011). Interestingly, TRAIL-R2 expression was associated with a microsatellite stable (MS-S/L) phenotype (p = 0.0003) and with absence of KRAS mutations (p = 0.0481). Conclusion: TRAIL-R1 expression was an independent prognostic marker for better survival in all CRC samples and even in the CRC group that received adjuvant therapy. The biological effects of TRAIL in CRC models, its enhancement of chemosensitivity towards standard chemotherapeutic agents and the effect of endogenous TRAIL receptor levels on survival make TRAIL an extremely attractive therapeutic target. [ABSTRACT FROM AUTHOR]

Published
2010
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29. Bortezomib Stabilizes Mitotic Cyclins and Prevents Cell Cycle Progression via Inhibition of UBE2Cin Colorectal Carcinoma

Author

Bavi, Prashant, Uddin, Shahab, Ahmed, Maqbool, Jehan, Zeenath, Bu, Rong, Abubaker, Jehad, Sultana, Mehar, Al-Sanea, Nasser, Abduljabbar, Alaa, Ashari, Luai H., Alhomoud, Samar, Al-Dayel, Fouad, Prabhakaran, Sarita, Hussain, Azhar R., and Al-Kuraya, Khawla S.

Abstract

Substantial evidence implicates the ubiquitin-conjugating enzyme E2C (UBE2C) gene, in several human cancers, including colorectal carcinoma (CRC). We therefore investigated the prognostic value of UBE2C alterations in CRC and UBE2C signaling in CRC cell lines. UBE2C protein expression and UBE2Cgene copy number were evaluated on clinical samples by immunohistochemistry and fluorescence in situhybridization in a TMA format. The effect of the proteasome inhibitor bortezomib and small-interfering RNA knockdown was assessed by apoptotic assays and immunoblotting. UBE2C dysregulation was associated with proliferative marker Ki-67, accumulation of cyclin A and B1, and a poor overall survival. UBE2C expression was an independent prognostic marker in early-stage (I and II) CRC. UBE2C depletion resulted in suppression of cellular growth and accumulation of cyclin A and B1. In vitro, bortezomib treatment of CRC cells caused inhibition of cell viability via down-regulation of UBE2C. UBE2C knockdown by bortezomib or transfection with specific small-interfering RNA against UBE2C also caused cells to be arrested at the G2/M level, leading to accumulation of cyclin A and cyclin B1. In vivo, a significant reduction in tumor volume and weight was noted in mice treated with a combination of subtoxic doses of oxaliplatin and bortezomib compared with treatment with oxaliplatin or bortezomib alone. Altogether, our results suggest that UBE2C and the ubiquitin-proteasome pathway may be potential targets for therapeutic intervention in CRC.

Published
2011
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30. Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer

Author

Carmela Martini, Jessica M. Logan, Alexandra Sorvina, Colin Gordon, Andrew R. Beck, Ben S-Y. Ung, Maria C. Caruso, Courtney Moore, Ashleigh Hocking, Ian R.D. Johnson, Ka Lok Li, Litsa Karageorgos, Ashley M. Hopkins, Adrian J. Esterman, Chelsea Huzzell, Robert D. Brooks, Joanna Lazniewska, Shane M. Hickey, Christie Bader, Emma Parkinson-Lawrence, Roberto Weigert, Michael J. Sorich, Prerna Tewari, Cara Martin, Sharon O'Toole, Mark Bates, Mark Ward, Bashir Mohammed, Helen Keegan, William Watson, Sophie Prendergast, Sheena Heffernan, Sarah NiMhaolcatha, Roisin O'Connor, Victoria Malone, Marguerite Carter, Katie Ryan, Nathan Brady, Andres Clarke, Filip Sokol, Sarita Prabhakaran, Jürgen Stahl, Sonja Klebe, Hemamali Samaratunga, Brett Delahunt, Stavros Selemidis, Kim L. Moretti, Lisa M. Butler, John J. O'Leary, Douglas A. Brooks, Martini, Carmela, Logan, Jessica M, Sorvina, Alexandra, Gordon, Colin, Beck, Andrew R, Ung, Ben SY, Caruso, Maria C, Moore, Courtney, Johnson, Ian RD, Li, Ka Lok, Karageorgos, Litsa, Esterman, Adrian J, Huzzell, Chelsea, Brooks, Robert D, Lazniewska, Joanna, Hickey, Shane M, Bader, Christie, Parkinson-Lawrence, Emma, Prabhakaran, Sarita, Moretti, Kim L, and Brooks, Doug A

Subjects
Pathology and Forensic Medicine
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. Refereed/Peer-reviewed

Published
2022

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