High Goblet Cell Count Is Inversely Associated with Ploidy Abnormalities and Risk of Adenocarcinoma in Barrett’s Esophagus

<div><p>Purpose</p><p>Goblet cells may represent a potentially successful adaptive response to acid and bile by producing a thick mucous barrier that protects against cancer development in Barrett's esophagus (BE). The aim of this study was to determine the relationship between goblet cells (GC) and risk of progression to adenocarcinoma, and DNA content flow cytometric abnormalities, in BE patients.</p><p>Experimental Design</p><p>Baseline mucosal biopsies (N=2988) from 213 patients, 32 of whom developed cancer during the follow up period, enrolled in a prospective dynamic cohort of BE patients were scored in a blinded fashion, for the total number (#) of GC, mean # of GC/crypt (GC density), # of crypts with ≥ 1 GC, and the proportion of crypts with ≥1 GC, in both dysplastic and non-dysplastic epithelium separately. The relationship between these four GC parameters and DNA content flow cytometric abnormalities and adenocarcinoma outcome was compared, after adjustment for age, gender, and BE segment length.</p><p>Results</p><p>High GC parameters were inversely associated with DNA content flow cytometric abnormalities, such as aneuploidy, ploidy >2.7N, and an elevated 4N fraction > 6%, and with risk of adenocarcinoma. However, a Kaplan-Meier analysis showed that the total # of GC and the total # crypts with ≥1 GC were the only significant GC parameters (p<0.001 and 0.003, respectively).</p><p>Conclusions</p><p>The results of this study show, for the first time, an inverse relationship between high GC counts and flow cytometric abnormalities and risk of adenocarcinoma in BE. Further studies are needed to determine if GC depleted foci within esophageal columnar mucosa are more prone to neoplastic progression or whether loss of GC occurs secondary to underlying genetic abnormalities.</p></div

Results of univariate analysis regarding goblet cell parameters in patients who did or did not progress to cancer.

<p>NC = No cancer</p><p>C = Cancer</p><p>^ǂ p-value: test for the risk difference between absent/present of the feature</p><p>Results of univariate analysis regarding goblet cell parameters in patients who did or did not progress to cancer.</p

Goblet Cell Counts and Risk of Adenocarcinoma, Per Patient Analysis (Kaplan-Meier Curves).

<p>In a per patient analysis, the Kaplan-Meier curves show an inverse association between risk of adenocarcinoma and averaged GC parameters in non-dysplastic biopsies in each patient: # GC (A), mean #GC/crypt (B), # crypts with ≥ 1 GC (C) and proportion of crypts with ≥ 1GC (D). P-values are from log-rank tests and have been adjusted for multiple comparison using the Benjamini & Hochberg method.</p

Goblet Cell Counts in Relationship to Aneuploidy.

<p>Non-dysplastic biopsies in patients with aneuploidy detected at baseline endoscopy have significantly lower # GC (A), mean #GC/crypt (B), # crypts with ≥ 1 GC (C) and proportion of crypts with ≥ 1GC (D) when compared to non-dysplastic biopsies in patients without aneuploidy at baseline endoscopy.</p

Goblet Cell Counts and Risk of Adenocarcinoma, Per Biopsy Analysis (Kaplan- Meier Curves).

<p>In a per biopsy analysis, the Kaplan-Meier curves show an inverse association between risk of adenocarcinoma and # GC (A), mean #GC/crypt (B), # crypts with ≥ 1 GC (C) and proportion of crypts with ≥ 1GC (D) in non-dysplastic biopsies from BE patients. P-values are from log-rank tests and have been adjusted for multiple comparison using the Benjamini & Hochberg method.</p

Clinical data of patients who did or did not progress to cancer.

<p>* combined nondysplastic and dysplastic</p><p>Clinical data of patients who did or did not progress to cancer.</p

Distribution of Patient Samples.

<p>Distribution of biopsies with or without columnar epithelium, and number of dysplastic and non-dysplastic crypts in patients who did, or did not, progress to cancer. 172 biopsies without columnar epithelium from the cancer group and 810 biopsies of columnar epithelium from the non-cancer group were excluded from the statistical analysis.</p