SOX9 and CDX2 Expression Predicts the Development of Barrett's Esophagus
Xuefeng Zhang, Mark Valasek, Oliver Chang, John Hart, Maria Westerhoff. University of Chicago, Chicago; University of Washington, Seattle
Background: The diagnosis of Barrett's Esophagus (BE) requires both endoscopic evidence of columnar mucosa (CM) and the presence of goblet cells (GC) by histology. The identification of GC can depend on the number of biopsy samples obtained and the location where the biopsies were taken. Several cellular signaling pathways responsible for modulation of intestinal differentiation have been shown to be involved in the development of metaplastic mucosa in BE, including sonic hedgehog (SHH), bone morphogenic protein 4 (BMP4), SOX9, and CDX2. In this study, we investigate whether the expression of these molecules in GC-negative CM from esophageal biopsies predicts the identification of GC in followup biopsies.
Design: Pathology databases from the Universities of Chicago and Washington were searched from 1990 to 2008 for esophageal biopsies containing CM in patients with endoscopic evidence of BE. Of these, 11 cases that were negative for GC on initial biopsies were found to have GC (without dysplasia) on followup biopsies (BE group; average age 54.9, GC detected at an average of 59.0 months after initial biopsy). Additionally, 25 cases that were initially negative for GC and remained negative on followup biopsies served as controls (average age 51.2, followed for an average of 49.4 months). Immunohistochemistry for CDX2, SOX9, BMP4, SHH, and p63 was performed on the initial biopsies and graded independently by at least 2 pathologists in a masked manner.
Results: CDX2 was positive in the CM of 6/11 cases in the BE group, and in 0/25 controls, resulting in a sensitivity of 55% and specificity of 100% (positive predictive value 100%, negative predictive value 83%). Focal and weak immunoreactivity for SOX9 was seen in most examples of CM; however, strong diffuse immunoreactivity for SOX9 was detected in 7/10 in the BE group and in 0/11 controls, giving rise to a sensitivity of 70% and specificity of 100% (positive predictive value 100%, negative predictive value 79%). p63 highlighted a focal basal-cell-like layer beneath the columnar mucosa in a few cases, but no difference existed between the two groups. SHH and BMP4 also showed no significant difference between the BE and control groups.
Conclusions: SOX9 and CDX2 are highly specific predictive markers for the identification of GC in followup biopsies of patients with GC-negative CM upon initial biopsy. These markers may be useful in identifying a subset of patients with CM who have a higher risk of developing BE and need closer followup.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 113, Monday Morning