Recurrent Transitional Cell Carcinoma Research Articles

Abstract 5546: Urine metabolomic biomarkers discovery for bladder cancer diagnostics

Abstract Current estimates in the United States for 2022 are about 81,180 new cases of bladder cancer diagnosis with about 17,100 deaths from the disease (American Cancer Society). Urothelial carcinoma, also known as transitional cell carcinoma (TCC), is the most common type of bladder cancer, approximately 70% of newly diagnosed TCC patients have non-muscle invasive bladder cancer (NMIBC) tumors. The gold standards for initial diagnosis and recurrence of TCC, cystoscopy and cytology, are both limited by their inability to visualize certain areas within the bladder or detect low grade tumors. Moreover, these tests are associated with false positive profiles, with potential for abnormal readouts even in individuals with no obvious signs of cancer. High recurrence rate predicates the need for constant monitoring of signs and symptoms associated with bladder disease following initial diagnosis, and non-invasive diagnostic modalities to detect both recurrent and primary early-stage tumors are a critical unmet need. In this study, comprehensive metabolomic profiling from human urine samples was used to identify and validate a panel of metabolites as potential biomarkers of bladder cancer. Urine samples from 439 total subjects (comprised of 66 bladder cancer, 119 history of bladder cancer but no bladder cancer at time of urine sampling, 58 hematuria subjects, 48 renal cell carcinoma, 58 prostate cancer, and 89 healthy subjects) were analyzed using a proprietary global untargeted metabolomic platform. A follow-up study to determine the reproducibility of the initial data set was conducted with 162 urine samples from subjects with bladder cancer that were either recurrent or primary, or with a negative diagnosis for bladder cancer with a previous history of bladder cancer or had hematuria or urinary voiding issues. Utilizing both data sets, eight biochemicals (lactate, gluconate, palmitoyl sphingomyelin, acetylcarnitine, choline phosphate, succinate, and adenosine) were identified as potential urine biomarkers for bladder cancer. In addition, 3-hydroxybutyrate (BHBA), 2-hydroxybutyrate (AHB), and adipate were identified as potential urine biomarkers for urological cancers. In total, 37 biochemicals have now been identified with having the potential to serve as urine bladder cancer biomarkers, and the majority of the biochemicals identified as biomarkers were associated with biochemical pathways previously shown to be perturbed in bladder tumors. The performance characteristics of the identified biochemicals in the detection of bladder cancer will be reported. Citation Format: Andrew J. Schwab, Matthew W. Mitchell, Edward D. Karoly, Rangaprasad Sarangarajan. Urine metabolomic biomarkers discovery for bladder cancer diagnostics. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5546.

Clinical and diagnostic observation of transitional cell carcinoma recurrence in the ureteral stump: a case report

Urothelial cancer of the upper urinary tract is quite rare and accounts for 5–10% of all cases of urothelial cancer. Radiation research methods, primarily computer and magnetic resonance imaging, are leading in monitoring and detecting recurrence after surgery on the organs of the urinary system. A rare clinical case of recurrence of transitional cell carcinoma of the upper urinary tract in the ureteral stump is presented. The article, with an emphasis on radiodiagnosis, outlines a step-by-step follow-up of a patient with primary cancer of the upper third of the ureter (рT2N0M0), who was hospitalized in the city clinical hospital for pain in the right lumbar region. During dynamic contrast enhancement multiparametric MRI, a recurrence of the disease was established with a lesion of the non-removed stump of the right ureter. Semiotic MR signs of recurrence of transitional cell carcinoma of the upper urinary tract are described. The recurrent tumor of the ureteral stump was characterized by a moderate hyperintense T2WI MR signal and an isointense T1WI MR signal. Our data indicate lower ADC values in the tumor when measured by a large ROI (937 mm2, versus 796 mm2 ROI with a small size). The dynamic contrast enhancement performed in our study showed intensive accumulation of the contrast by the recurrent tumor.

Survey of Mast Cell Density in Transitional Cell Carcinoma

Background & Objective:Transitional cell carcinoma (TCC) is the world's seventh most common tumor and forms more than 90% of urinary bladder tumors. Invasive tumors are associated with poor prognosis, even with surgical treatment and chemotherapy. Some studies have found that an increase in the number of mast cells in TCC is related to the tumor grade and its aggressiveness. This study investigated the relationship between mast cell density (MCD) and features of TCC (tumor stage, grade, prognosis, and recurrence). Methods:Fifty-one cases with TCC were selected, and MCD was determined by immunohistochemistry (IHC) and Giemsa staining. Mortality rate and tumor recurrence were recorded. Results:The MCD mean was higher in high-grade tumors than in low-grade tumors (in IHC method: 9.127 vs 5.296; in Giemsa method: 5.512 vs 2.608). Also, the MCD mean in dead patients was higher than in survived patients (in IHC method: 11.390 vs 6.211; in Giemsa method: 7.460 vs 3.35). Patients with tumor recurrence showed a higher MCD mean than those without recurrence (in IHC method: 9.395 vs 5.475; in Giemsa method: 5.715 vs 2.931). Conclusion:Using mast cell tryptase and Giemsa, MCD may be associated with a positive correlation with tumor grade in TCC. Correlations between MCD, recurrence, prognosis, and tumor stage are probably caused by the effect of tumor grade (all with P<0.05).

To Compare Frequency of Tumour Recurrence in Low Risk Transitional Cell Carcinoma of Bladder Between Single Dose Mitomycin C Instillation and Control Group

Background: Many regimes of intravesical therapy have been tried in attempt to reduce the recurrence rate of non muscle invasive bladder cancer, these generally require frequent attendance for instillation. Multiple non-comparative studies have demonstrated the favourable outcomes of the immediate treatment by instillation of mitomycin C after transurethral resection of bladder tumor (TURBT) in cases of non-muscle invasive Transitional Cell Carcinoma.Objective: To compare frequency of tumour recurrence in low risk transitional cell carcinoma of bladder between single dose Mitomycin C instillation and control group.Material and Methods: This study was conducted at urology departmentsaidu teaching hospital and Nawaz sharif kidney center swat. Study Design Quasi Experimental.Study Duration was (From: Feb 2018 to February 2019). Total 62 patients fulfilling the inclusion criteria were selected. Patient were divided between group A and B according to Non probability purposive sampling. TURBT was done in all patients. In those assigned to group A Mitomycin C 40mg was instilled through foleys catheter and clamped within 12 hrs of resection once haematuria has cleared. Mitomycin C was retained for 2 hrs and then foleys catheter was removed.Results: Mean age of patients in Group-A and in Group-B was 54.90±11.48 and 60.03±13.58 years respectively. In Group-A 1(3.2%) and in Group-B 9(29%) patients had recurrence after 3 months follow up time period. Recurrence rate of Group-B was significantly higher. i.e. (p-value=0.006).Conclusion: Results of this study showed the superiority of mitomycin C in patients with low risk non muscle invasive bladder cancer in terms of significantly lower recurrence rate as compared to that of control group. So, it can be said that single mitomycin C instillation significantly decrease recurrence in patients with low risk non muscle invasive bladder cancer.

Expression of Stem Cell Marker OCT4 and EGF Receptor Predict Recurrence in Transitional Cell Carcinoma of Bladder in Egyptian Patients

Expression of Stem Cell Marker OCT4 and EGF Receptor Predict Recurrence in Transitional Cell Carcinoma of Bladder in Egyptian Patients

Transitional cell carcinoma recurrence impacting intestinal diversion after radical cystectomy. Oncologic outcomes of a rare site of recurrence.

IntroductionTransitional cell carcinoma recurrence within an intestinal urinary diversion (TCCUD) after radical cystectomy (RC) is a rare condition with unknown origin, prognosis and treatment. The aim of this study was to describe treatment options and oncologic outcomes of this understudied site of recurrence in a multi-institutional case series.Material and methodsTCCUD relapse cases after RC were investigated in a retrospective, multi-institutional study. Surgical approach and adjuvant chemotherapy were discussed. Early and late complications were described according to the Clavien-Dindo classification. Kaplan-Meier method was used to assess progression-free and cancer-specific survival.ResultsA total of 19 patients were selected. The most common presentation was gross hematuria. The median interval between RC and TCCUD was 51.2 months. Fifteen patients (78.9%) underwent surgical excision, and two underwent concomitant radical nephroureterectomy. In 12 (63.1%) cases the site of TCCUD was the uretero-ileal anastomosis. Tumor invading the muscularis of the intestinal diversion was described in 10 (52.6%) cases. Surgical complications occurred in 7/15 (46.6%) patients, of these two with Clavien-Dindo Grade III. Four patients (21.0%) underwent adjuvant chemotherapy and two (10.5%) both chemotherapy and radiation therapy. During follow-up 15 patients (78.9%) presented with other sites of recurrence, with lymph nodes (21.0%) and liver (15.7%) being the most common localizations. Recurrence free and overall survival rates were 36.8% and 15.8%, and 56.5% and 24.2%, respectively at 12 and 18 months.ConclusionsMost patients with TCCUD have invasive disease and a substantial percentage experience upper tract cancer during their disease course. TCCUD is often the herald of advanced disease and systemic progression, with poor progression-free and overall survival rates.

The relationship between ABO blood group type and tumor grade, stage, recurrence and progression in transitional cell carcinoma of the bladder: A preliminary report

Objectives: ABO blood grouping is a well-proven prognostic factor in many malignancies. This study aims to study the association and impact of ABO blood group on disease recurrence and progression in bladder carcinoma. Material and methods: Patients with bladder carcinoma undergoing transurethral resection of bladder tumor (TURBT) were studied prospectively for at least 1-year follow-up for recurrence and progression of the disease. Demographic profile along with blood group was noted. Results: Two hundred patients were included in the study and 194 patients were included in the final analysis. Muscle-invasive bladder cancer was present in 39 (20.1%) patients and the high-grade tumor was present in 88 (45.3%) patients. There was no statistical significance between the association of blood grouping and grade ( p=0.29) and stage of the disease ( p=0.20). During the follow-up period, there were 100 (64.5%) recurrences and 15 (9.7%) patients with non-muscle-invasive bladder carcinoma had progression. The association of blood group with recurrence ( p=0.66) and progression ( p=0.11) of disease was not statistically significant. Conclusion: There is no association between bladder cancer and ABO blood group in terms of grade and stage of the disease. The recurrence and progression of the disease did not differ significantly in different blood groups. Level of Evidence: 2b

Results of Postoperative Instillation of Mitomycin C in Non Muscle Invasive Bladder Cancer after Complete Resection Versus BCG (Recurrence and Progression)

AbstractBackground: Intravesical immunotherapy or chemotherapy for non-muscle invasive bladder cancer is a well-established treatment for preventing or delaying tumour recurrence after tumour resection. However, up to 70% of patients may fail. New protocols and new intravesical agents with improved effectiveness are neededAim of Study: Is to evaluate the oncological outcome as regard progression, local recurrence and side effects of non-muscle invasive transitional cell carcinoma of the urinary bladder managed by complete resection followed by postop-erative intravesical instillation of Mitomycin C compared with BCG.Patients and Methods: This is a prospective study that included 51 patients with non-muscle invasive TCC bladder (Ta and T1) at Urology Department, Al-Azhar University hospitals between 2011 and 2015. Patients divided into two groups, the Mitomycin group received immediate MMC and periodic 6 doses of MMC and the other group, BCG received 6 doses of BCG one dose per week. Follow-up by cystoscope for two years at 3th, 6th, 9th, 12th, 18th, 24th month to detect the recurrence, progression and side effects.Results: The mean age of the patients was 60.58 (37 yrs. - 79 yrs.) in the MMC group and 61.76 (48 yrs-83 yrs) in the BCG group. The main comparison in this study is recurrence rate and progression rate of the tumor. Three patients (11.5%) had recurrence in the 1st year while four patients (15.4%) in the 2nd year with total recurrence seven patients (26.9%) in MMC group.In the BCG group, patients who had a recurrence in the 1st year were, two patients (8%) and three patients (12%) in the 2nd year with total recurrence, five patients (20%).The total progression in two years were 4 pts (15.38%) (One patient (3.8%) in the 1st year) (3 patients (11.5%) in the 2nd year) in the MMC group while were 4 pts (16%) (One patient (4%) in the 1st year) (year 3 patients (12%) in the 2nd year) in the BCG group.Conclusion: Our study confirmed the positive effect of immediate Mitomycin C intravesical instillation in patients who received periodic Mitomycin C instillation and either the positive effect of intravesical instillation of BCG in patients with non-muscle-invasive bladder tumors. Our present study showed that MMC and BCG equally reduced recurrence and progression in NMIBC patients while showed the superiority of MMC regarding to the adverse effects.

Clinical evaluation of nuclear matrix protein 22 as urinary marker of transitional cell carcinoma of bladder

OBJECTIVES. Biomarkers (BTA, NMP22, FDP etc.) have been and continue to be evaluated as adjuncts or substitutes for cystoscopy, which is invasive and uncomfortable for some patients. Nuclear matrix protein-22 (NMP22) is involved in the regulation of nuclear processes. The main objective of the present study is to evaluate the clinical utility of urinary NMP22 as a tumor marker in the follow-up of transitional cell carcinoma (TCC) of the bladder. MATERIALS AND METHODS. The study included 62 patients undergoing follow-up, who had had TCC of bladder but who were disease-free at the beginning of the study, as confirmed by cystoscopy. Urine samples were collected for urinary cytology and NMP22 test before the cystoscopy. All samples were processed according to the instructions provided with the manufacturer's kit instructions. Results. 12 cases of TCC recurrences were detected with biopsy. Cystoscopy was positive in 8 cases, NMP22 test was positive in 11 cases, and in only one case the cytopathology yielded positive results. In 14 cases NMP22 resulted as false positive. CONCLUSIONS. Urinary NMP22 appeared to be a potential tumor marker for detecting TCC of the bladder, which might rise the sensitivity of cystoscopy especially in high-grade cancer surveillance more than cytology might do.

P132 - Transitional cell carcinoma recurrence in intestinal urinary diversions: A multicentric cases series

P132 - Transitional cell carcinoma recurrence in intestinal urinary diversions: A multicentric cases series

Patterns of Recurrence in Upper Tract Transitional Cell Carcinoma: Imaging Surveillance.

The objective of our study was to evaluate recurrence patterns of upper tract transitional cell carcinomas (UT-TCCs) after radical nephroureterectomy (RNU). Sixty-eight patients (mean age, 78 years; 34 men and 34 women) with UT-TCC after having undergone RNU from 2001 to 2008 were included in this study. Radiologic examinations and clinical notes were reviewed to record tumor location, tumor morphology, histologic T stages and grades, lymphovascular invasion (LVI) status, and surgical procedures. Five-year imaging and clinical follow-up (2001-2013) findings were noted at 3, 6, 12, 18, 24, 36, 48, 60, and more than 60 months after RNU for recurrence pattern and tumor-free survival. Kaplan-Meier survival curves and Cox regression models were used to assess tumor-free survival and to perform a multivariate analysis. Forty-one postoperative recurrences were noted in 20 patients. The mean time to relapse was 16 months, and time to relapse ranged from 1 to 66 months. Tumor site (multifocal lesions involving both renal collecting system and ureter), tumor morphology (mass), T stage (muscle invasion [T2-T4]), histologic grade (grade 3), and the presence of LVI were identified as risk factors for postoperative recurrence in UT-TCC. T stage was the only independent risk factor. Urinary tract, lymph node, liver, bone, and lung recurrences were common in patients with UT-TCC and were detected most frequently at 3-24 months. Tumor site, tumor morphology, T stage, grade, and LVI status were associated with recurrence after RNU. T stage was the only independent predictor of tumor-free survival. Close surveillance for extra-urinary tract recurrences in high-risk groups and a shorter-interval follow-up of the urinary tract in low-risk patients with adjuvant chemotherapy are recommended. Identifying recurrence patterns in UT-TCC can aid in planning an effective tailored imaging surveillance strategy.

Recurrence and progression in nonmuscle invasive transitional cell carcinoma of urinary bladder treated with intravesical Bacillus Calmette-Guerin: A single center experience and analysis of prognostic factors.

Background:Intravesical Bacillus Calmette–Guerin (BCG) has been the standard of care for the prevention of nonmuscle invasive bladder cancer (NMIBC) recurrence following resection. Attempts to improve on the result by combining it with other agents have largely failed. This study addresses the result of BCG therapy in our patient population and compares the result with our combination BCG and interferon therapy published earlier.Materials and Methods:The medical records of patients diagnosed with NMIBC and treated with transurethral resection and intravesical BCG were reviewed. Univariate analysis was performed on most known prognostic factors. Results were compared to published data on the use of BCG and interferon from the same institution.Results:Thirty-one patients were identified. Median age was 66 (range 33–109), 80.6% were males. Fourteen patients (45%) had ≤ 3 tumors and 18 (58.1%) had T1 lesions. Four patients (12.9%) had Grade 3 tumors and 25 (80.6%) had Grade 2 tumors. One patient (3.2) had concurrent carcinoma in situ and 11 (35.5%) were treated upon initial diagnosis. At 5 years, the relapse-free survival was 61.3% (95% confidence interval (CI) 44.2–78.4%), progression-free survival was 85.6% (95% CI 73.3–97.9%), and overall survival was 93% (95% CI 84.1–100%). Comparison with the BCG and interferon data showed no significant difference.Conclusion:The result of BCG therapy in our patient population is similar to western reported data. Efficacy of BCG alone is equal to BCG and interferon within our institution.

Invasive Recurrent Transitional Cell Carcinoma of the Ethmoid Region in a Horse

Invasive Recurrent Transitional Cell Carcinoma of the Ethmoid Region in a Horse

Recurrence of isolated transitional cell carcinoma in an orthotopic ileal neobladder: A case report

Recurrent tumors inside an orthotopic ileal neobladder are rare, and only few cases have been reported in the literature. Herein, we report a case of recurrent transitional cell carcinoma in an orthotopic ileal neobladder discovered one and a half years after the operation.

Reply by Authors

No AccessJournal of UrologyAdult Urology1 Nov 2015Reply by Authors View All Author Informationhttps://doi.org/10.1016/j.juro.2015.05.108AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Reply by Authors." The Journal of Urology, 194(5), p. 1208 References 1 : Multicentric study comparing intravesical chemotherapy alone and with local microwave hyperthermia for prophylaxis of recurrence of superficial transitional cell carcinoma. J Clin Oncol2003; 21: 4270. Google Scholar © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 194Issue 5November 2015Page: 1208 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Expand All Advertisement PDF downloadLoading ...

Decreased expression of protein tyrosine phosphatase non-receptor type 12 is involved in the proliferation and recurrence of bladder transitional cell carcinoma.

Protein tyrosine phosphatase non-receptor type 12 (PTPN12) has been shown to be involved in the development of a number of types of carcinoma. However, the effect of PTPN12 on the proliferation and recurrence of human bladder transitional cell carcinoma (TCC) is unclear. The present study aimed to investigate the expression and function of PTPN12 in human TCC. Samples from 164 patients with TCC, in addition to 146 patients undergoing bladder surgery for indications other than TCC, were examined. PTPN12 protein expression was examined using immunohistochemistry and western blotting, and PTPN12 mRNA expression was examined using reverse transcription-quantitative polymerase chain reaction. PTPN12 expression was increased following transfection with the PTPN12-expressing, pcDEF3 vector, and PTPN12 expression was decreased by RNA interference, in four TCC cell lines. The proliferation of TCC cells was analyzed by a WST-1 assay and in xenografts on BALB/C nude mice. The effect of PTPN12 on tumor recurrence was analyzed by adhesion, migration and invasion assays in TCC cell lines. PTPN12 expression was significantly decreased in TCC tissues compared with that in normal urothelium, and the level of PTPN12 expression was negatively correlated with tumor size, pathological grade, clinical stage and tumor recurrence. Furthermore, decreased expression of PTPN12 significantly enhanced the proliferation of TCC cells in vitro and in vivo. TCC cells with lower levels of PTPN12 exhibited greater adhesion, migration and invasion. In conclusion, PTPN12 expression is downregulated in human TCC. Restoring PTPN12 activity may represent a novel therapeutic strategy for this disease.

Good survival in a patient with recurrent transitional cell carcinoma of the ovary: A case report of PET-CT for detection and follow-up.

Transitional cell carcinoma (TCC) of the ovary is a rare subtype of epithelial ovarian cancer. The present study reports the case of a 55-year-old patient from The Affiliated Tumor Hospital of Harbin Medical University (Harbin, Heilongjiang, China) who underwent successful surgery for recurrence of a TCC of the ovary with rectum metastases following the initial surgery and chemotherapy. Positron emission tomography/computed tomography (PET-CT) was used in the pre-operative detection of the tumor and the post-operative follow-up of the patient. To date, the patient has experienced 8 years of disease-free survival. The aim of the present study was to convey the good survival rate of the patient following recurrent TCC of the ovary, and the role of PET-CT in detection and follow-up, in order to aid in the future selection of appropriate diagnostic methods and therapies for this disease.

Prediction of bladder tumor relapse based on the risk factors and characteristics of the treatment.

Objectives. To investigate the possibility of predicting recurrence of bladder based on the clinical and morphological features of the disease and preoperative intravesical instillation of probiotic Aerococcus viridans 167. 190 patients operated for bladder have been observed for a period from 1 to 73 months (mean 35.2 months). In 51 patients one single preoperative intravesical instillation of probiotic Aerococcus viridans 167 was added to a standard treatment. Reported cases of recurrence of were used as a basis for the development of mathematical rules for predicting recurrences. These rules have been used to create a logistic regression and support vector machines. Of 190 patients, in 132 (69,5%) transitional cell carcinoma (TCC) in the stage T a -T 1 , in 58 (30,5%) - transitional cell papilloma of the bladder (TCP) was identified. Recurrences were detected in 52 (27.4%) patients, mean time of observation was 14.7 (1-50 months). In patients with TCC recurrence was observed in 36 (37%) of 96 patients not treated with probiotic instillation vs 7 (19%) of 36 after probiotic use (p> 0,05). In TCP group no significant signs of the instillation influence of probiotics on the number of relapses were revealed. Classification rules that can predict the risk of recurrence of bladder based on histological characteristics and application of probiotic were obtained. Preoperative instillation of probiotic Aerococcus viridans 167 in TCC TaT1 patients reduces the recurrence rate from 37% to 19% (p <0,05). Variables Number of tumors and Maximum tumor size, and their relationship are informative prognostic parameters. The rules obtained may be recommended to follow up patients after surgery for timely distinguishing group of patients with increased risk of bladder tumor recurrence.

Disseminated tuberculosis in a patient with recurrent transitional cell carcinoma of renal pelvis and bladder following intravesical BCG therapy: A report of a rare case

Bacillus Calmette-Guerin (BCG) has been used as an intravesical instillation for nonmuscle invasive (superficial) bladder cancer for the last 3 decades. Although intravesical BCG therapy is well-tolerated by most of the patients, adverse reactions have also been reported which are usually local, benign, and self-limited. Systemic complications such as miliary tuberculosis (TB) are very rare with few documented reports in literature. We hereby report a rare case of disseminated TB in bilateral lungs, adrenal, cervical, mediastinal, and para-aortic lymph nodes in a patient with recurrent transitional cell carcinoma (TCC) of renal pelvis and urinary bladder. Peculiar feature of this case was the development of TB 2 years following last BCG instillation, which is unlike most of the cases in the literature where TB developed within few weeks of last dose of BCG.

Abstract 305: Ultra-low coverage exome sequencing of FFPE tumor specimens identifies exposure to carcinogenic aristolochic acid

Abstract Dietary intake of Aristolochia plants containing aristolochic acid (AA, IARC Group 1 carcinogen), leads to renal disease and to recurrent urinary tract transitional cell carcinomas (TCC). Mutation screens identified frequent A&amp;gt;T transversions, alterations underrepresented in other cancer types, as the signature of AA exposure. AA-associated TCC is a preventable cancer yet millions are estimated at risk due to unregulated medicinal use of Aristolochia. Here we present an ultra-low coverage modification of whole-exome sequencing (ULC-WES) as a novel molecular epidemiology method that reliably detects the AA mutation signature in small amounts of DNA from FFPE tumor tissues and can identify new exposed populations. DNA was isolated from paraffin sections of 18 TCC tumors from endemic nephropathy (EN) patients from regions in Croatia and Bosnia linked to exposure to AA. Four non-EN upper tract TCCs were used as controls. 250 ng of DNA was used for sequencing libraries and exome enrichment (Nimblegen, Roche). Libraries were sequenced on Illumina HiSeq2500 at 10-12x coverage. After data processing, GATK was used to call single nucleotide variants (SNV). To assess platform independence, 7 samples were run on SOLID 5500XL (Life), using proprietary chemistry and pipeline for data processing and variant calling. Normal genetic variants were filtered out after SNV annotation. ULC-WES at 10x identified the A&amp;gt;T predominance in 17 of 18 EN tumors (94%), and at &amp;lt;10x coverage (3-9 reads per SNV) still detected the major A&amp;gt;T pattern in 14 (78%) samples. In contrast, the A&amp;gt;T presence was &amp;lt;8% in the control TCCs. We observed stochastic distribution of the A&amp;gt;T mutations in the genome (R^2=0.83 for mutation count correlated with the chromosome length) but also identified recurrent non-synonymous A&amp;gt;T mutations in tumor suppressors and oncogenes including TP53, ARID1A, BRCA1/2, AXIN1, GATA3 and NRAS, DNMT1, FLT3, CSF1R and PIK3CA. We next detected recurrent A&amp;gt;T mutations in a number of histone and DNA modifiers suggesting epigenetic deregulation of genome activity in the AA-associated TCCs. In 2 patients, pairs of distinct TCCs from the same surgery had markedly overlapping mutation patterns (624 SNVs shared between same-side pelvic and ureteric tumors in one case, and 191 shared between renal pelvic and bladder tumors in the other). Thus, ULC-WES provided evidence supporting the concept of tumor cell seeding along the urinary tract as a mechanism of TCC spread and recurrence. We conclude that ULC-WES is a sensitive and specific method to identify AA exposure in tumor tissue and is directly applicable to identification of new populations at risk. The method can ultimately facilitate evidence-based preventive measures in the affected regions. Acknowledgments: Genetic Services Platform, IARC; Genome Technology Center, NYU Langone Medical Center; NIH P01 ES04068, NIH Fogarty International Center 1R03TW007042, Croatian Ministry of Science. Citation Format: Xavier Castells, Sandra Karanovic, Magali Olivier, Maude Ardin, Florence Le Calvez-Kelm, Catherine Voegele, James McKay, Damir Dittrich, Karla Medak Tomic, Kathleen Dickman, Arthur P. Grollman, Bojan Jelakovic, Jiri Zavadil. Ultra-low coverage exome sequencing of FFPE tumor specimens identifies exposure to carcinogenic aristolochic acid. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 305. doi:10.1158/1538-7445.AM2014-305