High-fidelity DNA histograms in neoplastic progression in Barrett's esophagus

Yu, Chunhao; Zhang, Xiaoqi; Huang, Qin; Klein, Michael A.; Goyal, Raj K.

doi:10.1038/labinvest.3700531

Cited by 36 publications

(56 citation statements)

References 19 publications

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“…However, by virtue of identifying a small number of abnormal nuclei from the area of interest, image cytometry may identify much higher rates of rare aneuploid cells that are not detected by flow cytometry 41. For instance, Yu et al reported that more than two-thirds of BO without dysplasia (69%) and LGD (82%) samples have aneuploid populations 49. Similarly, Fang et al demonstrated that up to 13% of BO without dysplasia and 60% of LGD samples showed DNA content abnormality 50.…”

Section: Discussionmentioning

confidence: 99%

Diagnosis and risk stratification of Barrett’s dysplasia by flow cytometric DNA analysis of paraffin-embedded tissue

Choi

Tsai

Rabinovitch

et al. 2017

Gut

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This study demonstrates the promise of DNA flow cytometry using FFPE tissue in the diagnosis and risk stratification of dysplasia in BO. The presence of DNA content abnormality correlates with increasing levels of dysplasia, as 95% of HGD samples showed DNA content abnormality. DNA flow cytometry also identifies a subset of patients with LGD and IND who are at higher risk for subsequent detection of HGD or OAC.

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Section: Discussionmentioning

confidence: 99%

Diagnosis and risk stratification of Barrett’s dysplasia by flow cytometric DNA analysis of paraffin-embedded tissue

Choi

Tsai

Rabinovitch

et al. 2017

Gut

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“…This has been reported previously and attributed to the intrinsic characteristics of performing DNA ploidy analysis using thin tissue sections. 43,64 Thick tissue sections (e.g., 410 μm) create difficulty in nuclei segmentation, especially in situations of touching and overlapping nuclei. Therefore, biased sampling error could happen where smaller and isolated nuclei are preferred.…”

Section: Discussionmentioning

confidence: 99%

“…18,38,39 Nonetheless, the majority of other studies are still focusing on the well-established DNA density measurements using tissue sections (e.g., 3-7 μm), especially the use of the commercially available ACIS system (Automated Cellular Imaging System, Dako, Denmark) from a field of view (FoV) of tissue sections. [40][41][42][43][44] Under a microscope at × 40 magnification, a FoV is digitally captured followed by image analysis to locate nuclei and to measure the integrated optical density (IOD) for each nucleus. DNA content histogram for FoV can then be constructed.…”

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confidence: 99%

Whole slide image cytometry: a novel method to detect abnormal DNA content in Barrett's esophagus

Wang

McManus

Arthur

et al. 2015

Laboratory Investigation

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Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). Both low-grade dysplasia (LGD) and highgrade dysplasia (HGD) are associated with an increased risk of progression to EAC. However, histological interpretation and grading of dysplasia (particularly LGD) is subjective and poorly reproducible. This study has combined whole slide imaging with DNA image cytometry to provide a novel method for the detection of abnormal DNA content through image analysis of tissue sections. A total of 20 cases were evaluated, including 8 negative for dysplasia (NFD), 6 LGD, and 6 HGD. Feulgenstained esophageal sections were scanned in their entirety. Barrett's mucosa was interactively chosen for automatic nuclei segmentation where irrelevant cell types were ignored. The combined DNA content histogram for all nuclei within selected image regions was then obtained. In addition, three histogram measurements were computed, including xER-5C, 2cDI, and DNA-MG. Visual evaluation suggested the shape of DNA content histograms from NFD, LGD, and HGD cases exhibiting identifiable differences. The histogram measurements, xER-5C, 2cDI, and DNA-MG, were shown to be effective in differentiating metaplastic from dysplastic cases with statistical significance. Moreover, they also successfully separated NFD, LGD, and HGD patients with statistical significance. Whole slide image cytometry is a novel and effective method for the detection of abnormal DNA content in BE. Compared with histological review, it is more objective. Compared with flow cytometry and cytology-preparation image cytometry, it is low cost, simple to use, only requires a single 1 μm section, and facilitates selection of tissue and topographical correlation. Whole slide image cytometry can detect differences in DNA content between NFD, LGD, and HGD patients in this cross-sectional study. Abnormal DNA content detection by whole slide image cytometry is a promising biomarker of progression that could affect future diagnostics in BE.

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“…In some studies, aneuploidy heralds an aggressive genotype [42,[48][49][50]. DNA content abnormalities, similar to those found in LGD, occur in the basal portions of crypts in ND epithelium [51].…”

Section: Pathologic and Molecular Features Of Barrett's Esophagusmentioning

confidence: 95%

The Case for Endoscopic Treatment of Non-dysplastic and Low-Grade Dysplastic Barrett’s Esophagus

et al. 2010

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Non-dysplastic mucosa (ND-) in Barrett's esophagus (BE) shows clonal molecular aberrations, loss of cell cycle control, and other features of "neoplasia." These changes occur prior to morphologic expression of neoplasia (dysplasia). Morphologic evaluation of dysplasia is fraught with error, and, as a result, often leads to false-negative and false-positive diagnoses. Early "crypt dysplasia" is difficult to detect, and is often missed in routine biopsy specimens. Some studies show substantial progression rates of low-grade dysplasia (LGD), and crypt dysplasia, to esophageal adenocarcinoma (EAC). Dysplasia, even when fully developed, may, in certain circumstances, be difficult to differentiate from non-dysplastic (regenerating) BE. Radiofrequency ablation (RFA) is a safe and effective method for removing mucosa at risk of cancer. Given the difficulties of dysplasia assessment in mucosal biopsies, and the molecular characteristics of ND-BE, this technique should be considered for treatment of all BE patients, including those with ND or LGD. Post-ablation neo-squamous epithelium reveals no molecular abnormalities, and is biologically stable. Given that prospective randomized controlled trials of ablative therapy for ND-BE aiming at reducing EAC incidence and mortality are unlikely to be completed in the near future, endoscopic ablation is a valid management option. The success of RFA in achieving safe, uniform, reliable, and predictable elimination of BE allows surgeons to combine fundoplication with RFA. Currently, there is no type of treatment for dysplastic or non-dysplastic BE that achieves a complete response in 100% of patients, eliminates all risk of developing cancer, results in zero adverse events, is less expensive in terms of absolute costs than surveillance, is durable for 20+ years, or eliminates the need for surveillance. Regardless, RFA shows established safety, efficacy, durability, and cost-effective profiles that should be considered in the management of patients with non-dysplastic or low-grade dysplastic BE.

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High-fidelity DNA histograms in neoplastic progression in Barrett's esophagus

Cited by 36 publications

References 19 publications

Diagnosis and risk stratification of Barrett’s dysplasia by flow cytometric DNA analysis of paraffin-embedded tissue

Diagnosis and risk stratification of Barrett’s dysplasia by flow cytometric DNA analysis of paraffin-embedded tissue

Whole slide image cytometry: a novel method to detect abnormal DNA content in Barrett's esophagus

The Case for Endoscopic Treatment of Non-dysplastic and Low-Grade Dysplastic Barrett’s Esophagus

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