Anica Högner1, Hans Krause2, Burkhard Jandrig3, Mumtaz Kasim1, Tom Florian Fuller2, Martin Schostak3, Andreas Erbersdobler4, Andreas Patzak5, Ergin Kilic6. 1. Charité-Universitätsmedizin Berlin, Institut für Vegetative Physiologie, Charitéplatz 1, Berlin, Germany. 2. Charité-Universitätsmedizin Berlin, Klinik für Urologie, Charitéplatz 1, Berlin, Germany. 3. Universitätsklinikum Magdeburg, Klinik für Urologie und Kinderurologie, Leipziger Straße 44, Magdeburg, Germany. 4. Universitätsmedizin Rostock, Institut für Pathologie, Strempelstraße 14, Rostock, Germany. 5. Charité-Universitätsmedizin Berlin, Institut für Vegetative Physiologie, Charitéplatz 1, Berlin, Germany. Electronic address: andreas.patzak@charite.de. 6. Klinikum Leverkusen, Institut für Pathologie, Am Gesundheitspark 11, Leverkusen, Germany.
Abstract
OBJECTIVE: To identify the clinicopathological association of PBRM1 (Polybromo-1 gene) and VHL (von Hippel-Lindau gene) expression at mRNA and protein levels in clear cell renal cell carcinoma (ccRCC) and its role in tumor progression. PATIENTS AND METHODS: Immunohistochemical analysis, Western blotting and qPCR analysis of PBRM1 and VHL were performed on fresh-frozen ccRCC and adjacent normal tissue obtained from 70 patients who underwent radical nephrectomy. In addition, a tissue microarray (TMA) from specimens of 326 ccRCC patients was used to evaluate the effect of loss of PBRM1 and VHL immunohistological expression on clinicopathological features as well as patient survival. RESULTS: In frozen tissue, PBRM1 and VHL mRNA were significantly down-regulated in most ccRCC tumors (77.6%/80.6%). Simultaneous weak PBRM1 and VHL protein expression was observed in 21.4% of frozen tumors. In the TMA samples, weak PBRM1 and VHL immunohistochemical staining was observed in 60.4% of the cases and was correlated (P<0.001). The association of PBRM1 and VHL immunohistochemical expression with clinicopathological parameters depicts a variable picture: predominantly weak PBRM1 and VHL expression were significantly associated with higher Fuhrman grade (P = 0.012 and 0.024, respectively) but only weak VHL expression was associated with a higher pT stage (P = 0.023). PBRM1 expression did not affect the overall survival, whereas weak VHL expression was associated with decreased patient overall survival (P = 0.013). CONCLUSIONS: Our data suggest that reduced expression of PBRM1 and VHL is correlated with an increased tumor aggressiveness. Low VHL expression was identified as a risk factor for worse patient overall survival, independently from PBRM1 expression pattern.
OBJECTIVE: To identify the clinicopathological association of PBRM1 (Polybromo-1 gene) and VHL (von Hippel-Lindau gene) expression at mRNA and protein levels in clear cell renal cell carcinoma (ccRCC) and its role in tumor progression. PATIENTS AND METHODS: Immunohistochemical analysis, Western blotting and qPCR analysis of PBRM1 and VHL were performed on fresh-frozen ccRCC and adjacent normal tissue obtained from 70 patients who underwent radical nephrectomy. In addition, a tissue microarray (TMA) from specimens of 326 ccRCC patients was used to evaluate the effect of loss of PBRM1 and VHL immunohistological expression on clinicopathological features as well as patient survival. RESULTS: In frozen tissue, PBRM1 and VHL mRNA were significantly down-regulated in most ccRCC tumors (77.6%/80.6%). Simultaneous weak PBRM1 and VHL protein expression was observed in 21.4% of frozen tumors. In the TMA samples, weak PBRM1 and VHL immunohistochemical staining was observed in 60.4% of the cases and was correlated (P<0.001). The association of PBRM1 and VHL immunohistochemical expression with clinicopathological parameters depicts a variable picture: predominantly weak PBRM1 and VHL expression were significantly associated with higher Fuhrman grade (P = 0.012 and 0.024, respectively) but only weak VHL expression was associated with a higher pT stage (P = 0.023). PBRM1 expression did not affect the overall survival, whereas weak VHL expression was associated with decreased patient overall survival (P = 0.013). CONCLUSIONS: Our data suggest that reduced expression of PBRM1 and VHL is correlated with an increased tumor aggressiveness. Low VHL expression was identified as a risk factor for worse patient overall survival, independently from PBRM1 expression pattern.
Authors: Beatriz C Lopes; Cristine Z Braga; Fabrício V Ventura; Jéssica G de Oliveira; Edson M Kato-Junior; Newton A Bordin-Junior; Debora A P C Zuccari Journal: J Pers Med Date: 2021-01-06
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Authors: Svenja Bihr; Riuko Ohashi; Ariane L Moore; Jan H Rüschoff; Christian Beisel; Thomas Hermanns; Axel Mischo; Claudia Corrò; Jörg Beyer; Niko Beerenwinkel; Holger Moch; Peter Schraml Journal: Neoplasia Date: 2019-01-16 Impact factor: 5.715