Giuliano Morgantetti1, Keng Lim Ng2,3, Hemamali Samaratunga4, Handoo Rhee3, Glenda C Gobe2, Simon T Wood3. 1. Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, Brazil. 2. Translational Research Institute, University of Queensland Faculty of Medicine, Brisbane, Australia. 3. Department of Urology, Princess Alexandra Hospital, Brisbane, Australia. 4. Aquesta Pathology, Toowong, Brisbane, Australia.
Abstract
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a malignant renal neoplasm with a peculiar propensity to propagate as a contiguous tumor extension via the renal vein and inferior vena cava, occasionally reaching the right atrium. This intravascular tumor extension, often referred to as a tumor thrombus, represents the active growing front of the cancer. Prostate specific membrane antigen (PSMA), a glycoprotein that is extensively used in prostate cancer diagnostics, is a useful vascular marker for a variety of solid tumors. It is expressed in renal carcinomas. The aim of the current investigation was to analyse and compare the expression of PSMA at the growing front of the vena cava tumor extension with that found in the primary renal lesion. METHODS: Immunohistochemical (IHC) analysis of PSMA and CD34 was performed on archived paraffin embedded vena cava tumour thrombus tissue and matching renal tumours. These specimens were collected from radical nephrectomies of 10 patients with vena cava invasive (pT3b) ccRCC in a large tertiary hospital in Australia. Quantitative and qualitative morphometric analysis of PSMA IHC expression was performed with Aperio ImageScope morphometry using intensity and positive pixel counts of CD34 and PSMA from the IVC tumour slides and the corresponding renal tumour mass. RESULTS: PSMA and CD34 immunostaining were noted in the neovasculature of IVC tumour and renal tumour tissue. There was a higher PSMA/CD34 positive pixel count ratio noted in IVC tumour tissue when compared to renal tumour tissue. PSMA showed consistently increased expression in vena cava tumour, in comparison with the renal tumour mass. CONCLUSIONS: Intravascular venous tumour extension expresses PSMA more intensely compared to intrarenal tumour tissue neovasculature. Our data suggest a possible mechanism for PSMA in neoangiogenesis and local progression of ccRCC and therefore its usefulness as a biomarker of neoangiogenesis for future diagnostic and therapeutic advancements.
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a malignant renal neoplasm with a peculiar propensity to propagate as a contiguous tumor extension via the renal vein and inferior vena cava, occasionally reaching the right atrium. This intravascular tumor extension, often referred to as a tumor thrombus, represents the active growing front of the cancer. Prostate specific membrane antigen (PSMA), a glycoprotein that is extensively used in prostate cancer diagnostics, is a useful vascular marker for a variety of solid tumors. It is expressed in renal carcinomas. The aim of the current investigation was to analyse and compare the expression of PSMA at the growing front of the vena cava tumor extension with that found in the primary renal lesion. METHODS: Immunohistochemical (IHC) analysis of PSMA and CD34 was performed on archived paraffin embedded vena cava tumour thrombus tissue and matching renal tumours. These specimens were collected from radical nephrectomies of 10 patients with vena cava invasive (pT3b) ccRCC in a large tertiary hospital in Australia. Quantitative and qualitative morphometric analysis of PSMA IHC expression was performed with Aperio ImageScope morphometry using intensity and positive pixel counts of CD34 and PSMA from the IVC tumour slides and the corresponding renal tumour mass. RESULTS: PSMA and CD34 immunostaining were noted in the neovasculature of IVC tumour and renal tumour tissue. There was a higher PSMA/CD34 positive pixel count ratio noted in IVC tumour tissue when compared to renal tumour tissue. PSMA showed consistently increased expression in vena cava tumour, in comparison with the renal tumour mass. CONCLUSIONS: Intravascular venous tumour extension expresses PSMA more intensely compared to intrarenal tumour tissue neovasculature. Our data suggest a possible mechanism for PSMA in neoangiogenesis and local progression of ccRCC and therefore its usefulness as a biomarker of neoangiogenesis for future diagnostic and therapeutic advancements.
Authors: Stefanie Zschäbitz; Franziska Erlmeier; Christine Stöhr; Edwin Herrmann; Iris Polifka; Abbas Agaimy; Lutz Trojan; Philipp Ströbel; Frank Becker; Christian Wülfing; Peter Barth; Michael Stöckle; Michael Staehler; Christian Stief; Axel Haferkamp; Markus Hohenfellner; Stephan Macher-Göppinger; Bernd Wullich; Joachim Noldus; Walburgis Brenner; Frederik C Roos; Bernhard Walter; Wolfgang Otto; Maximilian Burger; Andres Jan Schrader; Yvonne Mondorf; Arndt Hartmann; Philipp Ivanyi; Sandra Steffens Journal: J Cancer Date: 2022-03-14 Impact factor: 4.207