Dataset Information

A Tissue Systems Pathology Assay for High-Risk Barrett's Esophagus.

ABSTRACT: Better methods are needed to predict risk of progression for Barrett's esophagus. We aimed to determine whether a tissue systems pathology approach could predict progression in patients with nondysplastic Barrett's esophagus, indefinite for dysplasia, or low-grade dysplasia.We performed a nested case-control study to develop and validate a test that predicts progression of Barrett's esophagus to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), based upon quantification of epithelial and stromal variables in baseline biopsies. Data were collected from Barrett's esophagus patients at four institutions. Patients who progressed to HGD or EAC in ?1 year (n = 79) were matched with patients who did not progress (n = 287). Biopsies were assigned randomly to training or validation sets. Immunofluorescence analyses were performed for 14 biomarkers and quantitative biomarker and morphometric features were analyzed. Prognostic features were selected in the training set and combined into classifiers. The top-performing classifier was assessed in the validation set.A 3-tier, 15-feature classifier was selected in the training set and tested in the validation set. The classifier stratified patients into low-, intermediate-, and high-risk classes [HR, 9.42; 95% confidence interval, 4.6-19.24 (high-risk vs. low-risk); P < 0.0001]. It also provided independent prognostic information that outperformed predictions based on pathology analysis, segment length, age, sex, or p53 overexpression.We developed a tissue systems pathology test that better predicts risk of progression in Barrett's esophagus than clinicopathologic variables.The test has the potential to improve upon histologic analysis as an objective method to risk stratify Barrett's esophagus patients. Cancer Epidemiol Biomarkers Prev; 25(6); 958-68. ©2016 AACR.

SUBMITTER: Critchley-Thorne RJ

PROVIDER: S-EPMC4891291 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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A Tissue Systems Pathology Assay for High-Risk Barrett's Esophagus.

Critchley-Thorne Rebecca J RJ Duits Lucas C LC Prichard Jeffrey W JW Davison Jon M JM Jobe Blair A BA Campbell Bruce B BB Zhang Yi Y Repa Kathleen A KA Reese Lia M LM Li Jinhong J Diehl David L DL Jhala Nirag C NC Ginsberg Gregory G DeMarshall Maureen M Foxwell Tyler T Zaidi Ali H AH Lansing Taylor D D Rustgi Anil K AK Bergman Jacques J G H M JJ Falk Gary W GW

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20160513 6

<h4>Background</h4>Better methods are needed to predict risk of progression for Barrett's esophagus. We aimed to determine whether a tissue systems pathology approach could predict progression in patients with nondysplastic Barrett's esophagus, indefinite for dysplasia, or low-grade dysplasia.<h4>Methods</h4>We performed a nested case-control study to develop and validate a test that predicts progression of Barrett's esophagus to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), bas ...[more]

PMID: 27197290

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Project description:Background & aimsPrediction of progression risk in Barrett's esophagus (BE) may enable personalized management. We aimed to assess the adjunct value of a tissue systems pathology test (TissueCypher) performed on paraffin-embedded biopsy tissue, when added to expert pathology review in predicting incident progression, pooling individual patient-level data from multiple international studies METHODS: Demographics, clinical features, the TissueCypher risk class/score, and progression status were analyzed. Conditional logistical regression analysis was used to develop multivariable models predicting incident progression with and without the TissueCypher risk class (low, intermediate, high). Concordance (c-) statistics were calculated and compared with likelihood ratio tests to assess predictive ability of models. A risk prediction calculator integrating clinical variables and TissueCypher risk class was also developed.ResultsData from 552 patients with baseline no (n = 472), indefinite (n = 32), or low-grade dysplasia (n = 48) (comprising 152 incident progressors and 400 non-progressors) were analyzed. A high-risk test class independently predicted increased risk of progression to high-grade dysplasia/adenocarcinoma (odds ratio, 6.0; 95% confidence interval, 2.9-12.0), along with expert confirmed low-grade dysplasia (odds ratio, 2.9; 95% confidence interval, 1.2-7.2). Model prediction of progression with the TissueCypher risk class incorporated was significantly superior than without, in the whole cohort (c-statistic 0.75 vs 0.68; P < .0001) and the nondysplastic BE subset (c-statistic 0.72 vs 0.63; P < .0001). Sensitivity and specificity of the high risk TissueCypher class were 38% and 94%, respectively.ConclusionsAn objective tissue systems pathology test high-risk class is a strong independent predictor of incident progression in patients with BE, substantially improving progression risk prediction over clinical variables alone. Although test specificity was high, sensitivity was modest.

Project description:Background & aimsNonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested to protect against esophageal adenocarcinoma (EAC). This study examined the effect of NSAIDs on the risk of developing Barrett's esophagus (BE), the precursor lesion to EAC.MethodsWe conducted a case-control study among eligible patients scheduled for either elective esophagogastroduodenoscopy (EGD) or recruited from primary care clinics to undergo a study EGD. We compared 323 patients with BE (296 nondysplastic and 27 dysplastic) with 2 separate control groups: 1347 patients from the elective EGD group (endoscopy controls) and 502 patients from the primary care group (primary care controls) with no endoscopic or histopathologic BE. Use of aspirin products and 23 nonaspirin NSAIDs was ascertained from detailed, self-reported questionnaires. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression models.ResultsThere were no significant differences in self-reported NSAID use between all BE cases and all controls (58.2% vs 54.6%; P = .33); this was seen for aspirin products (43.0% vs 37.4%; P = .08) and nonaspirin NSAIDs (7.7% vs 8.9%; P = .46). These findings persisted in the multivariable model for any NSAIDs (adjusted OR, 0.89; 95% CI, 0.75-1.28), aspirin (adjusted OR, 1.16; 95% CI, 0.90-1.51), and nonaspirin NSAIDs (adjusted OR, 0.88; 95% CI, 0.55-1.39). Use of a combination of aspirin and nonaspirin NSAIDs was reported in 7.4% of cases and 8.3% of controls, and a nonsignificant inverse association with BE was seen (adjusted OR, 0.70; 95% CI, 0.44-1.11). There was no significant association between BE and daily NSAID use (adjusted OR, 1.03; 95% CI, 0.78-1.37). Similar findings were observed for comparisons involving nondysplastic or dysplastic BE cases, and endoscopy or primary care control groups separately or combined.ConclusionsThe use of NSAIDs was not associated with a reduced risk of BE. It is likely that the protective mechanism of NSAIDs on EAC occurs subsequent to the development of BE.

Dataset Information

A Tissue Systems Pathology Assay for High-Risk Barrett's Esophagus.

Publications

A Tissue Systems Pathology Assay for High-Risk Barrett's Esophagus.

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