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MP28-20 PATHOLOGICAL VALIDATION OF ADJUVANT ANTI - FIBROBLAST GROWTH FACTOR RECEPTOR 3 (FGFR3) FOR PERSONALIZED TREATMENT OF BLADDER CANCER
THE JOURNAL OF UROLOGYâ
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Vol. 191, No. 4S, Supplement, Sunday, May 18, 2014
promising to guide decision making on adjuvant anti-FGFR3 therapy after RC because it appeared homogeneous in RC and cancer positive node samples. Based on the results from the TUR-specimens, the deep part of the tumor also needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. Source of Funding: YN receives grant from the European Urological Scholarship Programme, and with a funding from the GSK laboratories.
Kidney Cancer: Basic Research II Moderated Poster Sunday, May 18, 2014
10:30 AM-12:30 PM
Source of Funding: none
MP29-01 MP28-20
INCREASED EXPRESSION OF PREGNANCY UP-REGULATED NON-UBIQUITOUS CALMODULIN KINASE IS ASSOCIATED WITH POOR PROGNOSIS IN CLEAR CELL RENAL CELL CARCINOMA
PATHOLOGICAL VALIDATION OF ADJUVANT ANTI - FIBROBLAST GROWTH FACTOR RECEPTOR 3 (FGFR3) FOR PERSONALIZED TREATMENT OF BLADDER CANCER
Song Wu*, Hongbin Mei, Zhiming Cai, Shenzhen, China, People’s Republic of
Yann NEUZILLET*, Laura MERTENS, Amsterdam, Netherlands; Shahrokh SHARIAT, Dallas, TX; Peter BOSTROM, Tuomas MIRTTI, Turku, Finland; Arthur SAGALOWSKY, Raheela ASHFAQ, Dallas, TX; Annegien BROEKS, Michiel VAN, DER HEIJDEN, Dennis PETERS, Chantall CURIAL, Jeroen DE JONG, Simon HORENBLAS, Amsterdam, Netherlands; Carolyn HURST, Darren TOMLINSON, Margaret KNOWLES, Leeds, United Kingdom; Bharati BAPAT, Michael JEWETT, Alexandre ZLOTTA, Toronto, Canada; Joyce SANDERS, Amsterdam, Netherlands; Yair LOTAN, Dallas, TX; Theo VAN DER KWAST, Toronto, Canada; Bas VAN RHIJN, Amsterdam, Netherlands
INTRODUCTION AND OBJECTIVES: The aims of this study were to evaluate the clinical significance and potential prognostic value of pregnancy up-regulated non-ubiquitous calmodulin kinase (PNCK) in clear cell renal cell carcinoma (ccRCC) patients. METHODS: The expression of PNCK mRNA was determined in 24 paired samples of ccRCCs and adjacent normal tissues using realtime RT-PCR. The expression of PNCK was determined in 248 samples of ccRCCs and 92 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between PNCK expression and the clinical features of ccRCC. RESULTS: The mRNA level of PNCK was significantly higher in tumorous tissues than in the adjacent non-tumorous tissues (p<0.001). An immunohistochemical analysis of 92 paired tissue specimens showed that PNCK expression was higher in tumorous tissues than in the adjacent non-tumorous tissues (p<0.001). Moreover, there was a significant correlation between the PNCK expression and various clinicopathological parameters such as Fuhrman grade (p ¼ 0.011), tumor size (p<0.001), T stage (p<0.001) and N stage (p ¼ 0.015). Patients with higher PNCK expression had shorter overall survival time than those with lower PNCK expression (p<0.001). Multivariate analysis indicated that PNCK expression was an independent predictor for poor survival of ccRCC patients. CONCLUSIONS: To our knowledge, this is the first study that determines the relationship between PNCK and prognosis in ccRCC. We found that increased PNCK expression is associated with poor prognosis in ccRCC. PNCK may represent a novel prognostic marker for ccRCC.
INTRODUCTION AND OBJECTIVES: Activating Fibroblast Growth Factor Receptor 3 (FGFR3) mutations frequently occur in nonmuscle invasive bladder cancer (BC), whereas these mutations were poorly studied in patients with more advanced disease. In vitro studies suggest that anti-FGFR3 treatment slows down tumor-growth. We evaluated possible FGFR3 mutation heterogeneity in the non-invasive and invasive compartments of tumors obtained by trans-urethral resection (TUR) and by radical cystectomy (RC) including corresponding cancer positive nodes. METHODS: We identified paired samples from 61 primary TUR procedures (from 2 hospitals; 34 T1 and 27 T2 BC) among 494 cN0M0 RC specimens (from 4 hosptals). pN+ was found in 155/494 (31%) cases. Paired RC and cancer positive node samples were available for reliable FGFR3 mutation analysis in 117 (75%) patients. DNA was isolated from formalin-fixed paraffin-embedded tissue and FGFR3 mutation analysis was done using a multiplex PCR primer extension-based method (SNaPShot). RESULTS: We found 13/34 and 8/27 FGFR3 activating mutations in T1 and T2-TUR samples, respectively. In T1-TUR, the same 13 mutations were observed in superficial and invasive parts of the tumor. In T2-TUR, 4/8 mutations were not detected in the invasive part. In 4 tumors (one with mutation), we analyzed multiple samples from the same part of that tumor and found no differences among these samples. We found 62/494 FGFR3 mutations in RC specimens, of which 53 were pN0. The presence of a FGFR3 mutation was associated with pN0 (P¼0.002) at RC. We found a FGFR3 mutation in 6 out of 117 analyzed positive nodes. The same mutation was detected in the RC specimen. In the remaining 111 cases, RC and node samples were both wild type (specificity: 100%). CONCLUSIONS: The FGFR3 mutation was extremely rare in patients with cancer-positive nodes. FGFR3 mutation status seems
Source of Funding: none
MP29-02 INCREASED EXPRESSION OF ARYL HYDROCARBON RECEPTOR IN CLEAR CELL RENAL CELL CARCINOMA AND INFILTRATING LYMPHOCYTES: IMPLICATIONS FOR CANCER INVASION, PROGNOSIS AND TUMOR IMMUNITY Masaru Ishida*, Shuji Mikami, Takeo Kosaka, Ryuichi Mizuno, Eiji Kikuchi, Akira Miyajima, Ken Nakagawa, Yasunori Okada, Mototsugu Oya, Tokyo, Japan INTRODUCTION AND OBJECTIVES: Aryl hydrocarbon receptor (AhR) is involved in xenobiotic-induced toxicity, and it is also
e304
Vol. 191, No. 4S, Supplement, Sunday, May 18, 2014
promising to guide decision making on adjuvant anti-FGFR3 therapy after RC because it appeared homogeneous in RC and cancer positive node samples. Based on the results from the TUR-specimens, the deep part of the tumor also needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. Source of Funding: YN receives grant from the European Urological Scholarship Programme, and with a funding from the GSK laboratories.
Kidney Cancer: Basic Research II Moderated Poster Sunday, May 18, 2014
10:30 AM-12:30 PM
Source of Funding: none
MP29-01 MP28-20
INCREASED EXPRESSION OF PREGNANCY UP-REGULATED NON-UBIQUITOUS CALMODULIN KINASE IS ASSOCIATED WITH POOR PROGNOSIS IN CLEAR CELL RENAL CELL CARCINOMA
PATHOLOGICAL VALIDATION OF ADJUVANT ANTI - FIBROBLAST GROWTH FACTOR RECEPTOR 3 (FGFR3) FOR PERSONALIZED TREATMENT OF BLADDER CANCER
Song Wu*, Hongbin Mei, Zhiming Cai, Shenzhen, China, People’s Republic of
Yann NEUZILLET*, Laura MERTENS, Amsterdam, Netherlands; Shahrokh SHARIAT, Dallas, TX; Peter BOSTROM, Tuomas MIRTTI, Turku, Finland; Arthur SAGALOWSKY, Raheela ASHFAQ, Dallas, TX; Annegien BROEKS, Michiel VAN, DER HEIJDEN, Dennis PETERS, Chantall CURIAL, Jeroen DE JONG, Simon HORENBLAS, Amsterdam, Netherlands; Carolyn HURST, Darren TOMLINSON, Margaret KNOWLES, Leeds, United Kingdom; Bharati BAPAT, Michael JEWETT, Alexandre ZLOTTA, Toronto, Canada; Joyce SANDERS, Amsterdam, Netherlands; Yair LOTAN, Dallas, TX; Theo VAN DER KWAST, Toronto, Canada; Bas VAN RHIJN, Amsterdam, Netherlands
INTRODUCTION AND OBJECTIVES: The aims of this study were to evaluate the clinical significance and potential prognostic value of pregnancy up-regulated non-ubiquitous calmodulin kinase (PNCK) in clear cell renal cell carcinoma (ccRCC) patients. METHODS: The expression of PNCK mRNA was determined in 24 paired samples of ccRCCs and adjacent normal tissues using realtime RT-PCR. The expression of PNCK was determined in 248 samples of ccRCCs and 92 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between PNCK expression and the clinical features of ccRCC. RESULTS: The mRNA level of PNCK was significantly higher in tumorous tissues than in the adjacent non-tumorous tissues (p<0.001). An immunohistochemical analysis of 92 paired tissue specimens showed that PNCK expression was higher in tumorous tissues than in the adjacent non-tumorous tissues (p<0.001). Moreover, there was a significant correlation between the PNCK expression and various clinicopathological parameters such as Fuhrman grade (p ¼ 0.011), tumor size (p<0.001), T stage (p<0.001) and N stage (p ¼ 0.015). Patients with higher PNCK expression had shorter overall survival time than those with lower PNCK expression (p<0.001). Multivariate analysis indicated that PNCK expression was an independent predictor for poor survival of ccRCC patients. CONCLUSIONS: To our knowledge, this is the first study that determines the relationship between PNCK and prognosis in ccRCC. We found that increased PNCK expression is associated with poor prognosis in ccRCC. PNCK may represent a novel prognostic marker for ccRCC.
INTRODUCTION AND OBJECTIVES: Activating Fibroblast Growth Factor Receptor 3 (FGFR3) mutations frequently occur in nonmuscle invasive bladder cancer (BC), whereas these mutations were poorly studied in patients with more advanced disease. In vitro studies suggest that anti-FGFR3 treatment slows down tumor-growth. We evaluated possible FGFR3 mutation heterogeneity in the non-invasive and invasive compartments of tumors obtained by trans-urethral resection (TUR) and by radical cystectomy (RC) including corresponding cancer positive nodes. METHODS: We identified paired samples from 61 primary TUR procedures (from 2 hospitals; 34 T1 and 27 T2 BC) among 494 cN0M0 RC specimens (from 4 hosptals). pN+ was found in 155/494 (31%) cases. Paired RC and cancer positive node samples were available for reliable FGFR3 mutation analysis in 117 (75%) patients. DNA was isolated from formalin-fixed paraffin-embedded tissue and FGFR3 mutation analysis was done using a multiplex PCR primer extension-based method (SNaPShot). RESULTS: We found 13/34 and 8/27 FGFR3 activating mutations in T1 and T2-TUR samples, respectively. In T1-TUR, the same 13 mutations were observed in superficial and invasive parts of the tumor. In T2-TUR, 4/8 mutations were not detected in the invasive part. In 4 tumors (one with mutation), we analyzed multiple samples from the same part of that tumor and found no differences among these samples. We found 62/494 FGFR3 mutations in RC specimens, of which 53 were pN0. The presence of a FGFR3 mutation was associated with pN0 (P¼0.002) at RC. We found a FGFR3 mutation in 6 out of 117 analyzed positive nodes. The same mutation was detected in the RC specimen. In the remaining 111 cases, RC and node samples were both wild type (specificity: 100%). CONCLUSIONS: The FGFR3 mutation was extremely rare in patients with cancer-positive nodes. FGFR3 mutation status seems
Source of Funding: none
MP29-02 INCREASED EXPRESSION OF ARYL HYDROCARBON RECEPTOR IN CLEAR CELL RENAL CELL CARCINOMA AND INFILTRATING LYMPHOCYTES: IMPLICATIONS FOR CANCER INVASION, PROGNOSIS AND TUMOR IMMUNITY Masaru Ishida*, Shuji Mikami, Takeo Kosaka, Ryuichi Mizuno, Eiji Kikuchi, Akira Miyajima, Ken Nakagawa, Yasunori Okada, Mototsugu Oya, Tokyo, Japan INTRODUCTION AND OBJECTIVES: Aryl hydrocarbon receptor (AhR) is involved in xenobiotic-induced toxicity, and it is also