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ABSTRACT: Objective. To evaluate the relationship between osteopontin (OPN) in serum and plasma and parathyroid hormone-related protein (PTHrP) in serum, plasma and tumour tissue, and to assess the prognostic impact of OPN and PTHrP in human renal cell carcinoma (RCC). Material and methods. The study included 269 patients with RCC. In 189 patients, immunohistochemical (IHC) PTHrP tumour tissue expression was evaluated, and OPN and PTHrP in serum were assessed. In 80 patients, plasma OPN and PTHrP were analysed. Tumour type, TNM stage, nuclear grade and RCC-specific survival were also registered. In a sub-group, IHC expression of CD 31 was assessed. The prognostic information of the factors was analysed using uni- and multivariate analyses. Results. The median OPN level was 2.3 times higher in plasma than in serum. Serum OPN was significantly higher in patients with papillary RCC compared to clear cell RCC and chromophobe RCC. Both serum and plasma OPN levels were positively correlated to TNM stage and nuclear grade. Multivariate analysis showed that serum and plasma OPN levels were independent prognostic factors for RCC-specific survival, along with TNM stage. Immunohistochemical expression of PTHrP associated to TNM stage but not to nuclear grade or serum OPN. Furthermore, IHC expression of PTHrP was positively correlated to serum PTHrP but inversely to tumour CD31 expression. Plasma PTHrP was increased in 20% of the patients and related to TNM stage but not to nuclear grade. Plasma OPN was significantly higher in patients with increased PTHrP levels, compared to those with normal levels. Conclusion. Plasma OPN levels differed between RCC types, and in clear cell RCC, both serum and plasma OPN levels were independent predictors of survival. We found no evidence for prognostic value related to circulating levels or the IHC expression of PTHrP.
Acta oncologica (Stockholm, Sweden) 06/2012; · 2.27 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the prognostic information of soluble carbonic anhydrase (CA) IX expression in renal cell carcinoma (RCC).
Serum CA IX was analysed in 361 patients. Tumour type, TNM stage, nuclear grade, and RCC-specific survival were assessed. Serum and immunohistochemical expression were compared.
Median serum CA IX expression was 141 (range 2-4, 181) pg/ml. Levels were significantly higher in 287 patients with clear cell, compared to 40 papillary (p<0.001) and 22 oncocytoma (p=0.002), but not to 12 chromophobe RCC (p=0.35). Serum CA IX in clear cell RCC was positively correlated to TNM stage (p=0.002). There was a positive trend between serum and immunohistochemical CA IX expression. In a multivariate analysis of clear cell RCC, TNM stage and nuclear grade were independent prognostic factors.
Serum CA IX was higher in clear cell RCC compared to other RCC types. In clear cell RCC, serum CA IX correlated to TNM stage, but not survival.
Anticancer research 07/2010; 30(7):2953-7. · 1.73 Impact Factor
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ABSTRACT: Hypoxia-inducible factor (HIF)-2alpha is upregulated in hypoxia or by inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene. In a number of malignancies, increased HIF-2alpha expression may indicate worse prognosis. The aim of this study was to evaluate the prognostic information of HIF-2alpha mRNA expression in renal cell carcinoma (RCC).
HIF-2alpha mRNA was quantified by real time polymerase chain reaction (rt-PCR) in tumour tissue samples from 202 patients. Samples from 50 corresponding kidney cortex tissue were analysed as controls. mRNA levels were evaluated in relation to tumour cell type, TNM stage, nuclear grade and disease specific survival.
The levels of HIF-2alpha mRNA were significantly higher in 168 clear cell (c)RCC than in 23 papillary (p)RCC (p < 0.001) or 11 chromophobe (ch)RCC (p < 0.006). Among cRCC there was an inverse correlation between HIF-2alpha mRNA levels and TNM stage I and II-IV tumours (p=0.01), and nuclear grade (p = 0.006). After a median follow-up time of 99 months (range 34-247), 106 patients had died of RCC. No correlation of HIF-2alpha mRNA to survival was observed. A multivariate analysis of prognostic factors in cRCC showed that TNM stage alone was an independent predictor of prognosis; HIF-2alpha mRNA levels did not add further prognostic information.
The results demonstrated that HIF-2alpha mRNA levels were higher in cRCC compared to pRCC and chRCC. Furthermore, HIF-2alpha mRNA levels were inversely related to TNM stage and nuclear grade in cRCC.
Acta oncologica (Stockholm, Sweden) 04/2009; 48(6):909-14. · 2.27 Impact Factor
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ABSTRACT: To evaluate the prognostic information of carbonic anhydrase (CA) IX expression in patients with renal cell carcinoma (RCC), as increased expression of CA IX is correlated with a worse prognosis in several malignancies.
CA IX expression was assessed in RCC tumours from 228 patients, using a tissue microarray technique on archival material. The expression was related to RCC cell type, Tumour-Node-Metastasis (TNM) stage, nuclear grade and survival.
CA IX expression was significantly higher (P < 0.001) in 183 conventional than in 31 papillary RCC and 14 chromophobe RCC. For conventional RCC there was no correlation of CA IX expression with TNM stage or nuclear grade. To evaluate the prognostic information conventional RCC tumours were subdivided arbitrarily into three groups according to the CA IX expression, of 0-10%, 11-90% and 91-100% expression, respectively. Patients with tumours with 0-10% expression had a less favourable prognosis than those with 11-90% and 91-100% expression (P = 0.012, and 0.001), respectively. A multivariate analysis of prognostic factors for patients with conventional RCC showed that TNM stage, nuclear grade and CA IX were independent predictors of prognosis.
These results show that CA IX expression is higher in conventional than other RCC cell types; furthermore, patients with conventional RCC with low CA IX expression had a less favourable prognosis.
BJU International 09/2007; 100(3):556-60. · 2.84 Impact Factor
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ABSTRACT: Intratumoural microvessel density (MVD) has prognostic significance in selected neoplasms. To evaluate the prognostic information of MVD in renal cell carcinoma (RCC) we assessed the immunohistochemical expression of CD31 in 208 tumours using the tissue microarray technique. The expression was related to tumour cell type, TNM stage, nuclear grade and survival. CD31 expression was significantly (p < 0.001) higher in 167 conventional RCCs (clear cell) compared to 28 papillary RCCs. In conventional RCC, CD31 expression was inversely correlated to TNM stage (p = 0.024) and nuclear grade (p = 0.010). To evaluate the impact of CD31 expression on tumour-specific survival, the conventional RCC tumours were subdivided into quartiles according to the CD31 expression. In univariate analysis, patients with tumours in the quartile with the highest expression had a more favourable prognosis (p = 0.01) compared to those with lower CD31 expression. A multivariate analysis of prognostic factors in conventional RCC showed that TNM stage and nuclear grade were independent predictors of prognosis, but CD31 expression did not add further prognostic information.
Tumor Biology 02/2007; 28(3):158-64. · 1.94 Impact Factor
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ABSTRACT: To evaluate the prognostic potential of endoglin (CD105) expression in human renal cell carcinoma (RCC), as endoglin is a cell membrane glycoprotein expressed in tumour-associated vascular endothelium and a marker of angiogenesis; intratumoral microvessel density assessed by endoglin staining has prognostic significance in some neoplasms.
Tumour samples from 210 patients with RCC (168 conventional), diagnosed between 1982 and 1997, were assessed using the tissue microarray technique with immunohistochemical staining for endoglin. The expression of endoglin was related to clinical variables and survival.
Of the tumours, 75% expressed endoglin, and in conventional RCC the expression was inversely correlated to the Tumour-Node-Metastasis (TNM) stage (P = 0.008) and nuclear grade (P = 0.01). There was no correlation between endoglin expression and gender, age, tumour size or cell type. Patients with conventional RCC and high endoglin expression had a more favourable prognosis than those with tumours with lower expression (P = 0.04). A multivariate analysis of prognostic factors showed that TNM stage and nuclear grade were independent predictors of prognosis. Endoglin expression did not add further prognostic information.
These results indicate that endoglin expression is inversely related to stage and grade in RCC, and that it is associated with prognosis.
BJU International 05/2006; 97(4):706-10. · 2.84 Impact Factor
