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High Androgen Receptor mRNA Expression Is Independently Associated with Prolonged Cancer-Specific and Recurrence-Free Survival in Stage T1 Bladder Cancer.

ABSTRACT: INTRODUCTION:High-risk non-muscle-invasive bladder cancer (NMIBC) remains challenging given the high probability of progression. Given that the androgen receptor (AR) has been discussed as a possible factor in the development and progression of bladder cancer, we investigated the predictive value of AR in stage pT1 NMIBC. MATERIALS AND METHODS:We retrospectively analyzed the clinical data and AR mRNA expression in 296 patients with stage pT1 NMIBC who underwent a transurethral resection of the bladder. The mRNA expression of the AR transcript variants 1 (AR1) and 2 (AR2) was measured by reverse transcription quantitative real-time polymerase chain reaction. AR expression was also correlated to KRT5 and KRT20 mRNA expression. RESULTS:Kaplan-Meier analysis indicated that high AR1 mRNA expression ?35.47 is associated with statistically significant better recurrence-free survival (RFS) (P=.0007), progression-free survival (PFS) (P=.0420), and cancer-specific survival (CSS) (P=.0050). Multivariate Cox regression analysis revealed that high AR1 mRNA expression is an independent prognostic marker for RFS (P=.0029) and CSS (P=.0119). Spearman rank correlation revealed a significant positive association between mRNA expression of AR1 and KRT5 (rs: 0.3171, P<.0001) as well as a negative association with multifocal tumors (rs: 0.1478, P<.0109). No association was noted between AR1 expression and tumor grade, concomitant CIS, gender, tumor size, and KRT20 in patients with stage T1 NMIBC. CONCLUSIONS:AR mRNA expression can predict RFS and CSS in patients with stage T1 NMIBC. Further studies are necessary to refine the relevance of AR mRNA expression compared with immunohistochemically detectable AR expression.

SUBMITTER: Sikic D

PROVIDER: S-EPMC5367846 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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High Androgen Receptor mRNA Expression Is Independently Associated with Prolonged Cancer-Specific and Recurrence-Free Survival in Stage T1 Bladder Cancer.

Sikic Danijel D Breyer Johannes J Hartmann Arndt A Burger Maximilian M Erben Philipp P Denzinger Stefan S Eckstein Markus M Stöhr Robert R Wach Sven S Wullich Bernd B Keck Bastian B Wirtz Ralph M RM Otto Wolfgang W

Translational oncology 20170322 3

<h4>Introduction</h4>High-risk non-muscle-invasive bladder cancer (NMIBC) remains challenging given the high probability of progression. Given that the androgen receptor (AR) has been discussed as a possible factor in the development and progression of bladder cancer, we investigated the predictive value of AR in stage pT1 NMIBC.<h4>Materials and methods</h4>We retrospectively analyzed the clinical data and AR mRNA expression in 296 patients with stage pT1 NMIBC who underwent a transurethral res ...[more]

PMID: 28342317

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Project description:BackgroundWith the implementation of screening programs worldwide, diagnosis of early-stage colorectal cancer steadily increased, including T1 cancer. Current T1 cancer treatment does not differ according to anatomic location. We therefore compared the disease-free survival of T1 cancer arising from the rectum versus the colon.MethodsThe hospital-based study included subjects with T1 cancer at National Taiwan University Hospital from 2005 to 2014. Clinical, colonoscopy, and histopathology were reviewed for patients with a mean follow-up time of 7.1 (0.7-12.9) years. We conducted Kaplan-Meier analysis to compare the risk of recurrence by cancer location and Cox regression analysis to identify risk factors for T1 cancer recurrence.ResultsThe final cohort included a total of 343 subjects with T1 cancer (mean age, 64.9 ± 11.7 years; 56.1% male), of whom 25 underwent endoscopic resection alone. Of the subjects who underwent surgery, 50 had lymph node metastasis and 268 did not. Kaplan-Meier analysis showed that the risk of recurrence was higher in T1 rectal cancer than T1 colon cancer (p = .022). Rectal location and larger neoplasm size were independent risk factors for recurrence, with hazard ratios of 4.84 (95% confidence interval, 1.18-19.92), and 1.32 (95% confidence interval, 1.06-1.65), respectively. The occurrence of advanced histology did not differ between T1 rectal and colon cancers (p = .58).ConclusionT1 cancers arising from the rectum had less favorable recurrence outcomes than those arising from the colon. Further studies are needed to examine whether adjuvant radiotherapy or chemotherapy can reduce the risk of recurrence in T1 rectal cancer.Implications for practiceCurrent T1 colorectal cancer treatment and surveillance do not differ according to anatomic location. Clinical, colonoscopy, and histopathology were reviewed for 343 patients with T1 cancer with a mean follow-up time of 7.1 years. Kaplan-Meier analysis showed that the risk of recurrence was higher in T1 rectal cancer than T1 colon cancer. Moreover, the rectal location was an independent risk factor for recurrence. T1 cancers from the rectum had less favorable recurrence outcomes than those arising from the colon. It is critical to clarify whether adjuvant therapy or more close surveillance can reduce recurrence risk in T1 rectal cancer.

Project description:ImportanceCancer care guidelines recommend aligning surveillance frequency with underlying cancer risk, ie, more frequent surveillance for patients at high vs low risk of cancer recurrence.ObjectiveTo assess the extent to which such risk-aligned surveillance is practiced within US Department of Veterans Affairs facilities by classifying surveillance patterns for low- vs high-risk patients with early-stage bladder cancer.Design setting and participantsUS national retrospective cohort study of a population-based sample of patients diagnosed with low-risk or high-risk early-stage bladder between January 1, 2005, and December 31, 2011, with follow-up through December 31, 2014. Analyses were performed March 2017 to April 2018. The study included all Veterans Affairs facilities (n = 85) where both low-and high-risk patients were treated.ExposuresLow-risk vs high-risk cancer status, based on definitions from the European Association of Urology risk stratification guidelines and on data extracted from diagnostic pathology reports via validated natural language processing algorithms.Main outcomes and measuresAdjusted cystoscopy frequency for low-risk and high-risk patients for each facility, estimated using multilevel modeling.ResultsThe study included 1278 low-risk and 2115 high-risk patients (median [interquartile range] age, 77 [71-82] years; 99% [3368 of 3393] male). Across facilities, the adjusted frequency of surveillance cystoscopy ranged from 3.7 to 6.2 (mean, 4.8) procedures over 2 years per patient for low-risk patients and from 4.6 to 6.0 (mean, 5.4) procedures over 2 years per patient for high-risk patients. In 70 of 85 facilities, surveillance was performed at a comparable frequency for low- and high-risk patients, differing by less than 1 cystoscopy over 2 years. Surveillance frequency among high-risk patients statistically significantly exceeded surveillance among low-risk patients at only 4 facilities. Across all facilities, surveillance frequencies for low- vs high-risk patients were moderately strongly correlated (r = 0.52; P < .001).Conclusions and relevancePatients with early-stage bladder cancer undergo cystoscopic surveillance at comparable frequencies regardless of risk. This finding highlights the need to understand barriers to risk-aligned surveillance with the goal of making it easier for clinicians to deliver it in routine practice.

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Project description:BackgroundUrinary bladder carcinoma stage T1 is an unpredictable disease that in some cases has a good prognosis with only local or no recurrence, but in others can appear as a more aggressive tumor with progression to more advanced stages. The aim here was to investigate stage T1 tumors regarding MDM2 promoter SNP309 polymorphism, mutations in the p53 gene, and expression of p53 and p16 measured by immunohistochemistry, and subsequently relate these changes to tumor recurrence and progression. We examined a cohort of patients with primary stage T1 urothelial carcinoma of the bladder and their tumors.MethodsAfter re-evaluation of the original slides and exclusions, the study population comprised 141 patients, all with primary stage T1 urothelial carcinoma of the bladder. The hospital records were screened for clinical parameters and information concerning presence of histologically proven recurrence and progression. The paraffin-embedded tumor material was evaluated by immunohistochemistry. Any mutations found in the p53 gene were studied by single-strand conformation analysis and Sanger sequencing. The MDM2 SNP309 polymorphism was investigated by pyrosequencing. Multivariate analyses concerning association with prognosis were performed, and Kaplan-Meier analysis was conducted for a combination of changes and time to progression.ResultsOf the 141 patients, 82 had at least one MDM2 SNP309 G allele, and 53 had a mutation in the p53 gene, but neither of those anomalies was associated with a worse prognosis. A mutation in the p53 gene was associated with immunohistochemically visualized p53 protein expression at a cut-off value of 50%. In the group with p53 mutation Kaplan-Meier analysis showed higher rate of progression and shorter time to progression in patients with immunohistochemically abnormal p16 expression compared to them with normal p16 expression (p = 0.038).ConclusionsMDM2 SNP309 promoter polymorphism and mutations in p53 were not associated with worse prognosis in this cohort of patients with primary stage T1 urinary bladder carcinoma. However, patients with abnormal p16 expression and a mutated p53 gene had a higher rate of and a shorter time to progression, and p53 gene mutation was associated with an abnormal immunohistochemistry for p53 at a cut-off of 50%.

Dataset Information

High Androgen Receptor mRNA Expression Is Independently Associated with Prolonged Cancer-Specific and Recurrence-Free Survival in Stage T1 Bladder Cancer.

Publications

High Androgen Receptor mRNA Expression Is Independently Associated with Prolonged Cancer-Specific and Recurrence-Free Survival in Stage T1 Bladder Cancer.

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