p53 protein overexpression in low grade dysplasia (LGD) in Barrett's esophagus: Immunohistochemical marker predictive of progression

OBJECTIVES: The presence of low grade dysplasia (LGD) within Barrett's esop hagus (BE) has a multitude of ramifications. Identification of markers that could risk stratify LGD would be of great clinical benefit. We aimed to pr ospectively evaluate the prognosis of the immunohistochemical overexpressio n of p53 protein in BE colocalized to LGD. METHODS: Consecutive BE patients in whom LGD was found had a repeat esophag ogastroduodenoscopy within 8-12 wk per an ongoing prospective study. At eac h esophagogastroduodenoscopy, a therapeutic scope was used in conjunction w ith the Seattle Biopsy Protocol. Patients were observed until development o f multifocal high grade dysplasia (mHGD), presence of an HGD dysplasia-asso ciated lesion or mass (DALM) lesion, or frank adenocarcinoma. p53 protein o verexpression was determined by computerized immunoquantitation using image analysis software on step serial-sectioned specimens of BE segment(s) harb oring LGD. Kaplan-Meier survival curves were made on the ability of p53 sta ining colocalized to areas of LGD to predict progression to mHGD, HGD DALM, or cancer during prospective follow-up. RESULTS: Forty-eight BE patients with LGD were observed for a mean of 41.2 +/- 22.5 months. During this period, five of 48 patients progressed to mHGD with a focus in which intramucosal. cancer could not be excluded (one), mH GD/DALM with one or more foci in which intramucosal cancer could not be exc luded (two), cancer (one), or mHGD (one). Twelve had persistent LGD and 31 had regressed to no dysplasia. p53 staining was positive and colocalized to areas of LGD in 4/31 of patients that regressed, 3/12 that persisted, and 3/5 that progressed. Kaplan-Meier curves differed significantly between p53 positive and negative patients for outcome defined as progression of LCD. CONCLUSIONS: p53 colocalization with LGD at index LGD diagnosis is a risk f actor for progression of LGD. This can potentially be used to risk stratify BE LGD patients in terms of surveillance intervals or enrollment into seco ndary pre vention studies. (C) 2001 by Am. Cell. of Gastroenterology.