Abstract OBJECTIVES: The frequency of progression from low grade dysplasia (LGD) to high grade dysplasia/carcinoma (HGD/CA) in Barrett’s esophagus (BE) varies among studies. Current assessment is made more difficult because of pathologists’ interobserver variability in diagnosing LGD. We recently conducted an interobserver study on LGD and reported a positive correlation between the extent of agreement among GI pathologists and progression of LGD. In the current study, we analyzed the immunohistochemical staining for p53 in patients diagnosed with LGD with known clinical outcome and interobserver agreement data. METHODS: Fixed, paraffin-embedded endoscopic biopsy specimens from 16 patients diagnosed with LGD in BE were immunostained for p53 (DO-7, Dako, Carpinteria, CA). Hematoxylin and eosin-stained and immunostained sections were examined in tandem to determine whether the LGD areas in question stained for p53. The p53 immunoreactivity was correlated with clinical progression and with the interobserver agreement among three GI pathologists. RESULTS: The overall mean follow-up was 23 months (range 2–84 months). LGD areas in seven of eight patients (88%) who progressed to HGD/CA stained positively for p53 compared to only two of eight nonprogressors (25%). A correlation with clinical progression was seen for p53 positivity ( p = 0.017; log-rank test), and for either p53 positivity or complete agreement among three GI pathologists on LGD diagnosis ( p = 0.014; log-rank test). The p53 staining demonstrated 88% sensitivity and 75% specificity for progression of LGD to HGD/CA. Adding complete interobserver agreement on LGD among three experienced GI pathologists to p53 positivity resulted in improved sensitivity with no change in specificity (100% and 75%, respectively). CONCLUSIONS: In conjunction with histological evaluation by GI pathologists for a diagnosis of LGD, immunohistochemical staining for p53 can be used as an adjunctive test, as it correlated with progression to HGD/CA in this series.