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.