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MP71-04 SINGLE NUCLEOTIDE POLYMORPHISMS ASSOCIATED WITH RECURRENCE AFTER TREATMENT OF NON-METASTATIC RENAL CELL CARCINOMA
THE JOURNAL OF UROLOGYâ
e916
Vol. 195, No. 4S, Supplement, Monday, May 9, 2016
MP71-03
MP71-04
DEVELOPMENT OF A CLEAR CELL RENAL CELL CARCINOMA XENOGRAFT MODEL: A CASE FOR THE USE OF BIOPSY TISSUE OVER SURGICAL TISSUE
SINGLE NUCLEOTIDE POLYMORPHISMS ASSOCIATED WITH RECURRENCE AFTER TREATMENT OF NON-METASTATIC RENAL CELL CARCINOMA
Yiyu Dong, Brandon J Manley*, A. Ari Hakimi, Maria F Becerra, Paul Russo, Jonathan A. Coleman, James J Hsieh, New York, NY
Justin Gregg*, Zachary Glaser, Curran Emeruwa, Johnson Wong, Christopher Johnson, Arturo Holmes, Loren Lipworth, Peter Clark, Todd Edwards, Nashville, TN
INTRODUCTION AND OBJECTIVES: The establishment of a personalized xenograft model using biopsy tissue as a minimally invasive method of tissue harvest, from patients with metastatic or high-risk clear cell renal cell carcinoma (ccRCC) could improve selection of targeted therapy. We examined the success of our xenograft models in regards to various tissue sources and methods of harvest. METHODS: 56 specimens were collected from 48 patients with primary or metastatic ccRCC who consented to inclusion in the study. After surgery (n¼35) or biopsy (n¼21), each specimen was transplanted subcutaneously either immediately or after cell culture into immunodeficient mice. Conformation of xenograft tumors using hematoxylin and eosin-stained formalin-fixed, paraffin-embedded tumor sections was done to assure concordance with each patient’s tumor. We used a two-tailed two proportion z-test to compare xenografts harvested from surgical vs biopsy tissue. RESULTS: Overall, 25 of the 56 tumor specimens were successfully growing tumor tissue in our immunodeficient mice. Table 1 shows these results based on type and site of tissue harvest. Analysis comparing successful xenografts by method of tissue harvest found biopsy tissue to be more successful compared to surgical tissue, 62% vs 34% (p ¼ 0.044). CONCLUSIONS: Our study demonstrated the improved engraftment of biopsy tissue over surgically resected tissue for xenograft model development. This finding is likely in part due to inherent selection of more aggressive tumors for those who have biopsies. We believe that a xenograft model based on biopsy tissue from a metastatic tumor will be more clinically relevant for patients with metastatic disease.
Source of Funding: Ruth L. Kirschstein National Research Service Award T32CA082088, NIH/NCI Cancer Center Support Grant P30 CA008748
INTRODUCTION AND OBJECTIVES: A number of factors are known to be associated with the diagnosis of renal cell carcinoma (RCC), including age, smoking, body mass index (BMI), and hypertension. Single nucleotide polymorphisms (SNPs) have previously been shown to be associated with the diagnosis and prognosis of RCC and the aforementioned risk factors. We aimed to determine if these SNPs were associated with disease recurrence after treatment of RCC. METHODS: Patients at our institution who were previously genotyped as part of a multi-institutional genome-wide association study were eligible. Those who had been treated for RCC and did not have metastatic disease at time of presentation or surgery were included. SNPs of interest were chosen based on published association with established RCC risk factors and inclusion in the previously used genotyping platform (43 SNPs, total). Demographic, pathologic, and recurrence information were extracted using validated algorithms and manual review from the de-identified electronic health record. SNPs of interest were tested for their association with local or distant RCC recurrence using separate multivariable logistic regression models for each SNP adjusting for tumor size, stage, histology, Fuhrman grade, and margin status. RESULTS: A total of 308 patients were included in the study. Median follow-up time was 3.5 years (STD 3.8) for the 303 patients with available data. Among these, 241/308 (78.2%) had all data points available. Forty out of 241 patients (16.6%) had disease recurrence during follow-up. Tumor characteristics included 195/ 241 (80.9%) clear cell RCCs, 160 (66.4%) with T1 disease, 44 (18.3%) with Fuhrman grade 1 pathology, 12 (5.0%) with positive margins, and average tumor size of 5.2cm. Of the tested variables, only tumor stage was associated with disease recurrence in all 43 multivariable models (p<0.01 for all). SNPs rs2237892-T (p¼0.02) and rs12983273-T (p¼0.03) were associated with recurrence (Table). CONCLUSIONS: Two SNPs previously associated with BMI (rs2237892-T) or RCC survival (rs12983273-T) are associated with RCC recurrence. Further studies including larger patient populations, time-dependent analyses and additional recurrence-related covariates are warranted.
Source of Funding: Data collection and analysis were supported in part by National Center for Advancing Translational Sciences/National institutes of Health grant UL1 TR000445.
e916
Vol. 195, No. 4S, Supplement, Monday, May 9, 2016
MP71-03
MP71-04
DEVELOPMENT OF A CLEAR CELL RENAL CELL CARCINOMA XENOGRAFT MODEL: A CASE FOR THE USE OF BIOPSY TISSUE OVER SURGICAL TISSUE
SINGLE NUCLEOTIDE POLYMORPHISMS ASSOCIATED WITH RECURRENCE AFTER TREATMENT OF NON-METASTATIC RENAL CELL CARCINOMA
Yiyu Dong, Brandon J Manley*, A. Ari Hakimi, Maria F Becerra, Paul Russo, Jonathan A. Coleman, James J Hsieh, New York, NY
Justin Gregg*, Zachary Glaser, Curran Emeruwa, Johnson Wong, Christopher Johnson, Arturo Holmes, Loren Lipworth, Peter Clark, Todd Edwards, Nashville, TN
INTRODUCTION AND OBJECTIVES: The establishment of a personalized xenograft model using biopsy tissue as a minimally invasive method of tissue harvest, from patients with metastatic or high-risk clear cell renal cell carcinoma (ccRCC) could improve selection of targeted therapy. We examined the success of our xenograft models in regards to various tissue sources and methods of harvest. METHODS: 56 specimens were collected from 48 patients with primary or metastatic ccRCC who consented to inclusion in the study. After surgery (n¼35) or biopsy (n¼21), each specimen was transplanted subcutaneously either immediately or after cell culture into immunodeficient mice. Conformation of xenograft tumors using hematoxylin and eosin-stained formalin-fixed, paraffin-embedded tumor sections was done to assure concordance with each patient’s tumor. We used a two-tailed two proportion z-test to compare xenografts harvested from surgical vs biopsy tissue. RESULTS: Overall, 25 of the 56 tumor specimens were successfully growing tumor tissue in our immunodeficient mice. Table 1 shows these results based on type and site of tissue harvest. Analysis comparing successful xenografts by method of tissue harvest found biopsy tissue to be more successful compared to surgical tissue, 62% vs 34% (p ¼ 0.044). CONCLUSIONS: Our study demonstrated the improved engraftment of biopsy tissue over surgically resected tissue for xenograft model development. This finding is likely in part due to inherent selection of more aggressive tumors for those who have biopsies. We believe that a xenograft model based on biopsy tissue from a metastatic tumor will be more clinically relevant for patients with metastatic disease.
Source of Funding: Ruth L. Kirschstein National Research Service Award T32CA082088, NIH/NCI Cancer Center Support Grant P30 CA008748
INTRODUCTION AND OBJECTIVES: A number of factors are known to be associated with the diagnosis of renal cell carcinoma (RCC), including age, smoking, body mass index (BMI), and hypertension. Single nucleotide polymorphisms (SNPs) have previously been shown to be associated with the diagnosis and prognosis of RCC and the aforementioned risk factors. We aimed to determine if these SNPs were associated with disease recurrence after treatment of RCC. METHODS: Patients at our institution who were previously genotyped as part of a multi-institutional genome-wide association study were eligible. Those who had been treated for RCC and did not have metastatic disease at time of presentation or surgery were included. SNPs of interest were chosen based on published association with established RCC risk factors and inclusion in the previously used genotyping platform (43 SNPs, total). Demographic, pathologic, and recurrence information were extracted using validated algorithms and manual review from the de-identified electronic health record. SNPs of interest were tested for their association with local or distant RCC recurrence using separate multivariable logistic regression models for each SNP adjusting for tumor size, stage, histology, Fuhrman grade, and margin status. RESULTS: A total of 308 patients were included in the study. Median follow-up time was 3.5 years (STD 3.8) for the 303 patients with available data. Among these, 241/308 (78.2%) had all data points available. Forty out of 241 patients (16.6%) had disease recurrence during follow-up. Tumor characteristics included 195/ 241 (80.9%) clear cell RCCs, 160 (66.4%) with T1 disease, 44 (18.3%) with Fuhrman grade 1 pathology, 12 (5.0%) with positive margins, and average tumor size of 5.2cm. Of the tested variables, only tumor stage was associated with disease recurrence in all 43 multivariable models (p<0.01 for all). SNPs rs2237892-T (p¼0.02) and rs12983273-T (p¼0.03) were associated with recurrence (Table). CONCLUSIONS: Two SNPs previously associated with BMI (rs2237892-T) or RCC survival (rs12983273-T) are associated with RCC recurrence. Further studies including larger patient populations, time-dependent analyses and additional recurrence-related covariates are warranted.
Source of Funding: Data collection and analysis were supported in part by National Center for Advancing Translational Sciences/National institutes of Health grant UL1 TR000445.