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STAG2 Is a Biomarker for Prediction of Recurrence and Progression in Papillary Non-Muscle-Invasive Bladder Cancer.

ABSTRACT: Purpose: Most bladder cancers are early-stage tumors known as papillary non-muscle-invasive bladder cancer (NMIBC). After resection, up to 70% of NMIBCs recur locally, and up to 20% of these recurrences progress to muscle invasion. There is an unmet need for additional biomarkers for stratifying tumors based on their risk of recurrence and progression. We previously identified STAG2 as among the most commonly mutated genes in NMIBC and provided initial evidence in a pilot cohort that STAG2-mutant tumors recurred less frequently than STAG2 wild-type tumors. Here, we report a STAG2 biomarker validation study using two independent cohorts of clinically annotated papillary NMIBC tumors from the United States and Europe.Experimental Design: The value of STAG2 immunostaining for prediction of recurrence was initially evaluated in a cohort of 82 patients with papillary NMIBC ("Georgetown cohort"). Next, the value of STAG2 immunostaining for prediction of progression to muscle invasion was evaluated in a progressor-enriched cohort of 253 patients with papillary NMIBC ("Aarhus cohort").Results: In the Georgetown cohort, 52% of NMIBC tumors with intact STAG2 expression recurred, whereas 25% of STAG2-deficient tumors recurred (P = 0.02). Multivariable analysis identified intact STAG2 expression as an independent predictor of recurrence (HR = 2.4; P = 0.05). In the progressor-enriched Aarhus cohort, 38% of tumors with intact STAG2 expression progressed within 5 years, versus 16% of STAG2-deficient tumors (P < 0.01). Multivariable analysis identified intact STAG2 expression as an independent predictor of progression (HR = 1.86; P = 0.05).Conclusions: STAG2 IHC is a simple, binary, new assay for risk stratification in papillary NMIBC. Clin Cancer Res; 24(17); 4145-53. ©2018 AACR.

SUBMITTER: Lelo A

PROVIDER: S-EPMC6125225 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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STAG2 Is a Biomarker for Prediction of Recurrence and Progression in Papillary Non-Muscle-Invasive Bladder Cancer.

Lelo Alana A Prip Frederik F Harris Brent T BT Solomon David D Berry Deborah L DL Chaldekas Krysta K Kumar Anagha A Simko Jeffry J Jensen Jørgen Bjerggaard JB Bhattacharyya Pritish P Mannion Ciaran C Kim Jung-Sik JS Philips George G Dyrskjøt Lars L Waldman Todd T

Clinical cancer research : an official journal of the American Association for Cancer Research 20180628 17

<b>Purpose:</b> Most bladder cancers are early-stage tumors known as papillary non-muscle-invasive bladder cancer (NMIBC). After resection, up to 70% of NMIBCs recur locally, and up to 20% of these recurrences progress to muscle invasion. There is an unmet need for additional biomarkers for stratifying tumors based on their risk of recurrence and progression. We previously identified <i>STAG2</i> as among the most commonly mutated genes in NMIBC and provided initial evidence in a pilot cohort th ...[more]

PMID: 29954776

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Project description:BACKGROUND:Non-muscle invasive bladder cancer patients are at high risk for tumour recurrence and progression, hence an intensive follow-up procedure is recommended which is costly. Identification of factors that are associated with the risk of recurrence and progression may enable personalized follow-up schedules. Obesity and diabetes mellitus may be associated with a worse prognosis, but the evidence is limited and inconsistent. Our objective was to determine the associations of BMI and diabetes mellitus with risks of recurrence and progression among non-muscle invasive bladder cancer patients. METHODS:A population-based cohort of patients diagnosed with non-muscle invasive bladder cancer between 1995 and 2010 was retrospectively identified from the Netherlands Cancer Registry and invited to participate in the Nijmegen Bladder Cancer Study (n = 1,433). Average weight during adult life, height, and diabetes mellitus diagnosis were self-reported by use of a questionnaire. Clinical follow-up data were retrieved from medical files. Associations were quantified using proportional hazard analyses. For all analyses, minimal adjustment sets were selected using a Directed Acyclic Graph. RESULTS:Fourteen percent of the patients indicated to be diagnosed with diabetes mellitus, and more than half was overweight (45%) or obese (9%). Compared to healthy weight, overweight and obesity were not associated with risk of recurrence (adjusted hazard ratio (HR) = 1.02; 95% confidence interval (CI): 0.86-1.22, and HR = 1.02; 95% CI: 0.76-1.38, respectively) and overall progression (HR = 1.04; 95% CI: 0.74-1.44, and HR = 1.20; 95% CI: 0.69-2.09, respectively). Also, no clear associations of diabetes mellitus with risk of recurrence (HR = 1.22; 95% CI: 0.98-1.54) and overall progression (HR = 1.16; 95% CI: 0.76-1.76) were found. CONCLUSION:Average BMI during adult life and diabetes mellitus were not clearly associated with risk of recurrence or progression in non-muscle invasive bladder cancer. Prospective cohort studies with detailed information on BMI and diabetes mellitus before and after diagnosis are needed to confirm these findings.

Dataset Information

STAG2 Is a Biomarker for Prediction of Recurrence and Progression in Papillary Non-Muscle-Invasive Bladder Cancer.

Publications

STAG2 Is a Biomarker for Prediction of Recurrence and Progression in Papillary Non-Muscle-Invasive Bladder Cancer.

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