pd-08.07: ureteroscopic management of transitional cell carcinoma

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well as a Cox’s proportional hazards re- gression model for multivariate testing. Results: Fascin expression was noted in 13/136 (10%) primary and 25/54 (46%) metastases (p0.001). Fascin expression was associated with high tumour stage (2/70 [3%] pT1 vs. 11/66 [17%] pT2/pT3; p0.008), high tumour grade (3/88 [3%] G1/G2 vs. 10/48 [21%] G3/G4; p0.002) and large tumour size (p0.001). In addi- tion, 8/13 (62%) RCCs with sarcomatoid morphology expressed fascin, compared with 5/123 (4%) RCCs without sarcoma- toid transformation (p0.001). After a median follow-up of 43 months metastatic disease was noted in 10/13 (77%) patients with fascin-positive RCCs, compared with 26/121 (21%) patients with fascin-negative RCCs (p0.001). Multivariate analysis proved pT-stage 1 (p0.001, risk ratio [RR]8.6, 95% confidence interval [CI]2.8-26.5), grade 2 (p0.001, RR12.7, 95% CI4.6-35.4), fascin ex- pression (p0.001, RR7.2, 95% CI3.0- 17.4) as independent predictors of meta- static disease. Conclusion: Fascin immunoreactivity was significantly associated with tumour stage, grade, and size, sarcomatoid transforma- tion as well as disease-free survival. Meta- static RCC tissue expressed fascin in al- most half of the cases, thus providing a promising molecular target for future can- cer therapy. PD-08.07 Ureteroscopic management of transitional cell carcinoma Thomas K, Henderson J, Wiseman O, DasGupta P, Glass J, Tiptaft R Guys and St Thomas’ NHS Foundation Trust, London, UK Introduction: Whilst nephro-ureterec- tomy remains the gold standard treatment for upper tract transitional cell carcinoma (TCC), there are a small subset of patients who benefit from ureteroscopic manage- ment of their disease (low volume disease, solitary kidney, co-morbidity). We present the management of such patients in our hospital. Methods: Patients were identified from a prospective database of all ureteroscopies for TCC and the notes analysed. Results: Over a 3 year period (February 2003-March 2006) complete data on 28 patients undergoing ureteroscopies for TCC performed was obtained. The median age was 70 years (27 – 89). There were twice as many males as females. All pa- tients had been biopsied, of the new pa- tients in this period, 9 had G1pTa, a fur- ther 9 G2pTa, and 2 were G3 pTa. The location of tumours were; 3 upper, 1 mid and 2 lower pole calyx, 9 renal pelvis, 5 upper, 4 mid and 6 distal ureteric. Most of the patients were on a surveillance sched- ule varying from 3 monthly to annual ac- cording to recurrence rates and volume of disease. 5 patients had a nephro-ureterec- tomy; 4 for extensive disease and 1 for aggressive histology. The indications for ureteroscopic management were; low vol- ume disease 8, co-morbidity 5, solitary kidney 6 and bilateral disease 3. One pa- tient who refused surgical and uretero- scopic treatment progressed to metastatic disease. Conclusion: Ureteroscopic management of upper tract TCC appears to be a safe treatment for selected patients, however, it remains a second line option after nephro-ureterectomy has been consid- ered. PD-08.08 VEGF, VEGF-R1 and VEGF-R2 mRNA expression profiles different between clear and papillary renal cell carcinoma. Importance for angiogenic therapies Ljungberg B 1 , Jacobsen J 1 , Grankvist K 2 , Rasmuson T 3 , Lindh G 1 , Ha ¨ggstro ¨m Rudolfsson S 1 1 Dept. of Surgical and Perioperative Sci- ences, Urology and Andrology; 2 Dept. of Medical Biosciences, Clinical Chemistry; 3 Dept. of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden Introduction: Renal cell carcinoma (RCC) is generally refractory to most medical ther- apy. One potentially useful therapeutic alter- native is inhibition of angiogenesis. In this study VEGF, VEGF-R1, and VEGF-R2 mRNA levels were examined in clinical context. Methods: VEGF, VEGF-R1, and VEGF-R2 mRNA levels were analyzed using quantita- tive RT-PCR. RNA was extracted from 84 conventional (clear cell) (cRCC), 20 papil- lary (pRCC), 6 chromophobe (chRCC), and 27 corresponding kidney cortex tissues. Results: There were higher VEGF, VEGF-R1, and VEGF-R2 mRNA levels in tumor com- pared with kidney cortex tissues. Among the RCC types, cRCC had higher VEGF levels than pRCC. In cRCC, VEGF-R2 levels were higher in stage I-II than in more advanced stages. In pRCC, VEGF and VEGF-R2 levels were higher in stage III compared with stage I-II tumors. In cRCC, patients with VEGF levels below the median had significantly shorter survival time compared with higher levels. In contrast, in pRCC, VEGF, VEGF-R1, as well as VEGF-R2 levels above the median were related to ad- verse survival. Using multivariate analysis in cRCCs, VEGF-R1 mRNA levels were the last factor to be omitted after stepwise elimination analysis. Conclusion: VEGF and its receptor status are associated with tumor stage and sur- vival, but were not independent prognostic factors. The results showed that different RCC types had different expression patterns of VEGF and receptor mRNA levels. We conclude that different pathways may be involved in the regulation of angiogenesis in the specific RCC types. Detailed knowledge of angiogenesis in RCC is essential when designing new treatment trials where angio- genesis inhibition is used. PD-08.09 Tumor VEGF and microvessel density in renal cell carcinoma Singh SK, Bhuvanesh N, Prasad R, Joshi K Post Graduate Institute of Medical Edu- cation and Research, Chandigarh, India Introduction: Vascular endothelial growth factor (VEGF) promotes angiogen- esis and plays an important role in tumor progression. Prognostic significance of VEGF expression and micro vessels den- sity (MVD) in renal cell carcinoma (RCC) is in investigational stage. Methods: Total 34 patients with RCC were included in this study. VEGF expres- sion in the tumor and normal looking re- nal parenchyma from the same nephrec- tomy specimen was assessed by western blot. VEGF expression in the tumor was also quantified by immuno-staining using mouse monoclonal anti VEGF antibody (Clone JH 121, Neomarker) according to Abdulrauf 1998. Tumor angiogenesis was quantified by counting intra-tumoral MVD after immuno-staining using monoclonal anti CD-34 antibody as per methods de- scribed by Weidner et al 1991. Results: VEGF expression in tumor was significantly higher as compared to that in normal appearing renal parenchyma (27.596.47 Vs 16.954.93; p0.001). VEGF expression in tumor was not related to tumor stage and grade. However all 6 high grade tumors and 6/7 (85%) high stage tumors had VEGF score more than 2, whereas 19/28 (67.8%) low grade and 20/27 (74%) low stage tumor had score more than 2. The difference was statistically not significant (p0.05). Low-grade tumors had significantly high MVD (252.7140.4 Vs 124.281; p0.039). A trend of positive correlation was observed between VEGF expression and MVD (r0.317, p0.07). Conclusions: Significantly high expression of VEGF in tumors, suggesting that RCC produces VEGF, may be responsible for high vascularity of RCC. Low MVD in high- grade tumors may be due to development PODIUM SESSIONS 30 UROLOGY 68 (Supplement 5A), November 2006

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well as a Cox’s proportional hazards re-gression model for multivariate testing.Results: Fascin expression was noted in13/136 (10%) primary and 25/54 (46%)metastases (p�0.001). Fascin expressionwas associated with high tumour stage(2/70 [3%] pT1 vs. 11/66 [17%] pT2/pT3;p�0.008), high tumour grade (3/88 [3%]G1/G2 vs. 10/48 [21%] G3/G4; p�0.002)and large tumour size (p�0.001). In addi-tion, 8/13 (62%) RCCs with sarcomatoidmorphology expressed fascin, comparedwith 5/123 (4%) RCCs without sarcoma-toid transformation (p�0.001). After amedian follow-up of 43 months metastaticdisease was noted in 10/13 (77%) patientswith fascin-positive RCCs, compared with26/121 (21%) patients with fascin-negativeRCCs (p�0.001). Multivariate analysisproved pT-stage �1 (p�0.001, risk ratio[RR]�8.6, 95% confidence interval[CI]�2.8-26.5), grade �2 (p�0.001,RR�12.7, 95% CI�4.6-35.4), fascin ex-pression (p�0.001, RR�7.2, 95% CI�3.0-17.4) as independent predictors of meta-static disease.Conclusion: Fascin immunoreactivity wassignificantly associated with tumour stage,grade, and size, sarcomatoid transforma-tion as well as disease-free survival. Meta-static RCC tissue expressed fascin in al-most half of the cases, thus providing apromising molecular target for future can-cer therapy.

PD-08.07Ureteroscopic management oftransitional cell carcinomaThomas K, Henderson J, Wiseman O,DasGupta P, Glass J, Tiptaft RGuys and St Thomas’ NHS FoundationTrust, London, UK

Introduction: Whilst nephro-ureterec-tomy remains the gold standard treatmentfor upper tract transitional cell carcinoma(TCC), there are a small subset of patientswho benefit from ureteroscopic manage-ment of their disease (low volume disease,solitary kidney, co-morbidity). We presentthe management of such patients in ourhospital.Methods: Patients were identified from aprospective database of all ureteroscopiesfor TCC and the notes analysed.Results: Over a 3 year period (February2003-March 2006) complete data on 28patients undergoing ureteroscopies forTCC performed was obtained. The medianage was 70 years (27 –89). There weretwice as many males as females. All pa-tients had been biopsied, of the new pa-tients in this period, 9 had G1pTa, a fur-ther 9 G2pTa, and 2 were G3 pTa. The

location of tumours were; 3 upper, 1 midand 2 lower pole calyx, 9 renal pelvis, 5upper, 4 mid and 6 distal ureteric. Most ofthe patients were on a surveillance sched-ule varying from 3 monthly to annual ac-cording to recurrence rates and volume ofdisease. 5 patients had a nephro-ureterec-tomy; 4 for extensive disease and 1 foraggressive histology. The indications forureteroscopic management were; low vol-ume disease 8, co-morbidity 5, solitarykidney 6 and bilateral disease 3. One pa-tient who refused surgical and uretero-scopic treatment progressed to metastaticdisease.Conclusion: Ureteroscopic managementof upper tract TCC appears to be a safetreatment for selected patients, however,it remains a second line option afternephro-ureterectomy has been consid-ered.

PD-08.08VEGF, VEGF-R1 and VEGF-R2 mRNAexpression profiles different betweenclear and papillary renal cellcarcinoma. Importance for angiogenictherapiesLjungberg B1, Jacobsen J1, Grankvist K2,Rasmuson T3, Lindh G1, HaggstromRudolfsson S1

1Dept. of Surgical and Perioperative Sci-ences, Urology and Andrology; 2Dept. ofMedical Biosciences, Clinical Chemistry;3Dept. of Radiation Sciences, Oncology,Umeå University, Umeå, Sweden

Introduction: Renal cell carcinoma (RCC)is generally refractory to most medical ther-apy. One potentially useful therapeutic alter-native is inhibition of angiogenesis. In thisstudy VEGF, VEGF-R1, and VEGF-R2 mRNAlevels were examined in clinical context.Methods: VEGF, VEGF-R1, and VEGF-R2mRNA levels were analyzed using quantita-tive RT-PCR. RNA was extracted from 84conventional (clear cell) (cRCC), 20 papil-lary (pRCC), 6 chromophobe (chRCC), and27 corresponding kidney cortex tissues.Results: There were higher VEGF, VEGF-R1,and VEGF-R2 mRNA levels in tumor com-pared with kidney cortex tissues. Among theRCC types, cRCC had higher VEGF levels thanpRCC. In cRCC, VEGF-R2 levels were higherin stage I-II than in more advanced stages. InpRCC, VEGF and VEGF-R2 levels were higherin stage III compared with stage I-II tumors. IncRCC, patients with VEGF levels below themedian had significantly shorter survival timecompared with higher levels. In contrast, inpRCC, VEGF, VEGF-R1, as well as VEGF-R2levels above the median were related to ad-verse survival. Using multivariate analysis incRCCs, VEGF-R1 mRNA levels were the last

factor to be omitted after stepwise eliminationanalysis.Conclusion: VEGF and its receptor statusare associated with tumor stage and sur-vival, but were not independent prognosticfactors. The results showed that differentRCC types had different expression patternsof VEGF and receptor mRNA levels. Weconclude that different pathways may beinvolved in the regulation of angiogenesis inthe specific RCC types. Detailed knowledgeof angiogenesis in RCC is essential whendesigning new treatment trials where angio-genesis inhibition is used.

PD-08.09Tumor VEGF and microvessel densityin renal cell carcinomaSingh SK, Bhuvanesh N, Prasad R, Joshi KPost Graduate Institute of Medical Edu-cation and Research, Chandigarh, India

Introduction: Vascular endothelialgrowth factor (VEGF) promotes angiogen-esis and plays an important role in tumorprogression. Prognostic significance ofVEGF expression and micro vessels den-sity (MVD) in renal cell carcinoma (RCC)is in investigational stage.Methods: Total 34 patients with RCCwere included in this study. VEGF expres-sion in the tumor and normal looking re-nal parenchyma from the same nephrec-tomy specimen was assessed by westernblot. VEGF expression in the tumor wasalso quantified by immuno-staining usingmouse monoclonal anti VEGF antibody(Clone JH 121, Neomarker) according toAbdulrauf 1998. Tumor angiogenesis wasquantified by counting intra-tumoral MVDafter immuno-staining using monoclonalanti CD-34 antibody as per methods de-scribed by Weidner et al 1991.Results: VEGF expression in tumor wassignificantly higher as compared to that innormal appearing renal parenchyma(27.59�6.47 Vs 16.95�4.93; p�0.001).VEGF expression in tumor was not relatedto tumor stage and grade. However all 6high grade tumors and 6/7 (85%) high stagetumors had VEGF score more than 2,whereas 19/28 (67.8%) low grade and20/27 (74%) low stage tumor had scoremore than 2. The difference was statisticallynot significant (p�0.05). Low-grade tumorshad significantly high MVD (252.7�140.4Vs 124.2�81; p�0.039). A trend of positivecorrelation was observed between VEGFexpression and MVD (r�0.317, p�0.07).Conclusions: Significantly high expressionof VEGF in tumors, suggesting that RCCproduces VEGF, may be responsible forhigh vascularity of RCC. Low MVD in high-grade tumors may be due to development

PODIUM SESSIONS

30 UROLOGY 68 (Supplement 5A), November 2006