Otto Jokelainen1, Sanna Pasonen-Seppänen2, Markku Tammi2, Arto Mannermaa3, Sirpa Aaltomaa4, Reijo Sironen5, Timo K Nykopp6. 1. Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland; Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland. Electronic address: otto.jokelainen@uef.fi. 2. Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland. 3. Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland; Biobank of Eastern Finland, Kuopio University Hospital, Kuopio, Finland. 4. Department of Surgery, Kuopio University Hospital, Kuopio, Finland. 5. Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland; Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland. 6. Department of Surgery, Kuopio University Hospital, Kuopio, Finland; Surgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
Abstract
PURPOSE: Hyaluronan, a major glycosaminoglycan of the extracellular matrix, can act as an oncogenic component of the tumor microenvironment in many human malignancies. We characterized the hyaluronan content of renal cell carcinomas (RCCs) and investigated its correlations with clinicopathological parameters and patient survival. PATIENTS AND METHODS: This retrospective study included data from 316 patients that had undergone surgery for RCC in Kuopio University Hospital in 2000 to 2013. The hyaluronan content of surgical tumor samples were histochemically stained with a biotinylated hyaluronan-specific affinity probe. The amount of tumor infiltrating lymphocytes was evaluated in each tumor. Kaplan-Meier and univariate and multivariate Cox-regression analyses were performed to estimate the impact of hyaluronan content on overall survival, disease-specific survival, and metastasis-free survival. RESULTS: Detectable cellular hyaluronan was associated with higher tumor grades and the presence of tumor infiltrating lymphocytes. Cellular hyaluronan identified a prognostically unfavourable subgroup among low-grade carcinomas. Multivariate analyses showed that measurable cellular hyaluronan was an independent negative prognostic factor for overall survival (hazard ratio [HR] 1.4; 95% confidence interval [CI]: 1.02-2.0; P = 0.039), Disease-specific survival (HR 2.07; 95% CI: 1.2-3.3; P = 0.002), and metastasis-free survival (HR 2.45; 95% CI: 1.37-4.4; P = 0.003). CONCLUSIONS: Cellular hyaluronan was significantly associated with unfavourable features and a poor prognosis in RCC. Further studies are needed to investigate the biological mechanism underlying hyaluronan accumulation in RCC.
PURPOSE:Hyaluronan, a major glycosaminoglycan of the extracellular matrix, can act as an oncogenic component of the tumor microenvironment in many humanmalignancies. We characterized the hyaluronan content of renal cell carcinomas (RCCs) and investigated its correlations with clinicopathological parameters and patient survival. PATIENTS AND METHODS: This retrospective study included data from 316 patients that had undergone surgery for RCC in Kuopio University Hospital in 2000 to 2013. The hyaluronan content of surgical tumor samples were histochemically stained with a biotinylated hyaluronan-specific affinity probe. The amount of tumor infiltrating lymphocytes was evaluated in each tumor. Kaplan-Meier and univariate and multivariate Cox-regression analyses were performed to estimate the impact of hyaluronan content on overall survival, disease-specific survival, and metastasis-free survival. RESULTS: Detectable cellular hyaluronan was associated with higher tumor grades and the presence of tumor infiltrating lymphocytes. Cellular hyaluronan identified a prognostically unfavourable subgroup among low-grade carcinomas. Multivariate analyses showed that measurable cellular hyaluronan was an independent negative prognostic factor for overall survival (hazard ratio [HR] 1.4; 95% confidence interval [CI]: 1.02-2.0; P = 0.039), Disease-specific survival (HR 2.07; 95% CI: 1.2-3.3; P = 0.002), and metastasis-free survival (HR 2.45; 95% CI: 1.37-4.4; P = 0.003). CONCLUSIONS: Cellular hyaluronan was significantly associated with unfavourable features and a poor prognosis in RCC. Further studies are needed to investigate the biological mechanism underlying hyaluronan accumulation in RCC.
Authors: Sergei Kusmartsev; Elizabeth Kwenda; Paul R Dominguez-Gutierrez; Paul L Crispen; Padraic O'Malley Journal: J Kidney Cancer VHL Date: 2022-04-16