Predictors of progression to cancer in Barrett's esophagus: baseline histology and flow cytometry identify low- and high-risk patient subsets

Abstract

Objective: Barrett's esophagus develops in 5-20% of patients with gastroesophageal reflux disease and predisposes to esophageal adenocarcinoma. The value of endoscopic biopsy surveillance is questioned because most patients do not develop cancer. Furthermore, observer variation in histological diagnosis makes validation of surveillance guidelines difficult because varying histological interpretations may lead to different estimated rates of progression. Thus, objective biomarkers need to be validated for use with histology to stratify patients according to their risk for progression to cancer.

Methods: We prospectively evaluated patients using a systematic endoscopic biopsy protocol with baseline histological and flow cytometric abnormalities as predictors and cancer as the outcome.

Results: Among patients with negative, indefinite, or low-grade dysplasia, those with neither aneuploidy nor increased 4N fractions had a 0% 5-yr cumulative cancer incidence compared with 28% for those with either aneuploidy or increased 4N. Patients with baseline increased 4N, aneuploidy, and high-grade dysplasia had 5-yr cancer incidences of 56%, 43%, and 59%, respectively. Aneuploidy, increased 4N, or HGD were detected at baseline in all 35 patients who developed cancer within 5 yr.

Conclusions: A systematic baseline endoscopic biopsy protocol using histology and flow cytometry identifies subsets of patients with Barrett's esophagus at low and high risk for progression to cancer. Patients whose baseline biopsies are negative, indefinite, or low-grade displasia without increased 4N or aneuploidy may have surveillance deferred for up to 5 yr. Patients with cytometric abnormalities merit more frequent surveillance, and management of high-grade dysplasia can be individualized.

Figure 1

(A) Cumulative incidence of cancer after baseline histological diagnoses of negative, indefinite, and low-grade dysplasia. (B) Cumulative incidence of cancer after baseline histological diagnoses of negative, indefinite, low-grade dysplasia combined and high-grade displasia. Tick marks indicate time of last follow-up endoscopy for patients without cancer at last endoscopy.

Figure 2

Cumulative incidence of cancer after baseline flow cytometric diagnoses of diploid, normal 4N, elevated 4N without aneuploidy, aneuploidy without elevated 4N, elevated 4N, and aneuploidy.

Figure 3

Cumulative incidence of cancer with histology and flow cytometry combined. (A) Negative, indefinite, or low-grade dysplasia with neither aneuploidy nor elevated 4N fractions or with either aneuploidy or elevated 4N. (B) Baseline high-grade dysplasia with neither aneuploidy nor elevated 4N or with either aneuploidy or elevated 4N.