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J Cancer 2013; 4(8):626-634. doi:10.7150/jca.6990 This issue Cite

Research Paper

Nuclear Nano-architecture Markers of Gastric Cardia and Upper Squamous Esophagus Detect Esophageal Cancer “Field Effect”

Kenneth E. Fasanella¹, Rajan K. Bista², Kevin Staton², Sumera Rizvi¹, Shikhar Uttam², Chengquan Zhao³, Antonia Sepulveda⁴, Randall E. Brand¹, Kevin McGrath¹, Yang Liu^1,2,5✉

1. Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;
2. Biomedical Optical Imaging Laboratory (BOIL), Departments of Medicine and Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;
3. Department of Pathology, Magee-Womens Hospital of University of Pittsburgh Medical Center Pittsburgh, Pennsylvania, USA;
4. Division of Gastrointestinal Pathology, Department of Pathology & Cell Biology, Columbia University, New York, New York, USA;
5. University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.

✉ Corresponding author: Yang Liu, PhD, Department of Medicine and Bioengineering, 5117 Centre Avenue, Hillman Cancer Center 2.32, Pittsburgh, Pennsylvania 15232, USA. E-mail: liuyedu; Tel: 412-6233751.

Abstract

Background: Barrett's esophagus (BE) affects up to 12 million Americans and confers an increased risk for development of esophageal adenocarcinoma (EAC). EAC is often fatal unless detected early. Given the high prevalence, high cost of surveillance and relatively low risk of most affected individuals, identification of high-risk patients for additional scrutiny, regular surveillance, or ablative therapy is crucial. The exploration of “field effect” by probing uninvolved esophageal mucosa to predict the risk of EAC has the potential as an improved surveillance and prevention strategy. In this study, we evaluate the ability of nuclear nano-architecture markers from normal squamous esophagus and gastric cardia to detect the “field effect” of esophageal dysplasia and EAC, and their response to endoscopic therapy.

Methods: Patients with normal esophagus, gastroesophageal reflux, BE and EAC were eligible for enrollment. We performed endoscopic cytology brushings of the gastric cardia, ~1-2 cm below the gastroesophageal junction, and of the normal squamous esophageal mucosa at ~20 cm from the incisors and standard cytology slides were made using Thinprep method. Optical analysis was performed on the cell nuclei of cytologically normal-appearing epithelial cells.

Results: The study cohort consisted of 128 patients. The nuclear nano-architecture markers detected the presence of esophageal dysplasia and EAC with statistical significance. The field effect does not exhibit a spatial dependence. These markers reverted toward normal in response to endoscopic therapy.

Conclusions: Optical analysis of gastric cardia and upper squamous esophagus represents a potentially viable method to improve risk stratification and ease of surveillance of patients with Barrett's esophagus and to monitor the efficacy of ablative therapy.

Keywords: nuclear architecture, nanoscale, esophagus, dysplasia, field effect.

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