P53 and Racemase Immunohistochemistry in the Evaluation of Glandular Atypia Versus Low Grade Dysplasia/Indefinite for Dysplasia in a Large Cohort of Patients with Barrett Esophagus
Robert Petras, Jennifer Jeung, Trang Ly, William Katzin. AmeriPath Institute of Gastrointestinal Pathology and Digestive Disease, Cleveland, OH
Background: Distinguishing regenerative atypia from low-grade dysplasia/indefinite for dysplasia (LGD/Ind) in Barrett esophagus (BE) is difficult. We have been using p53 and racemase (rac) immunohistochemistry (IHC) in this setting. The purpose of this study is to review the utility of IHC in the evaluation of glandular atypia in patients with BE, correlating staining with outcome.
Design: We searched the archives 2009-11 for patients with BE and p53 and rac IHC. Patients with a history of esophageal high grade dyplasia (HGD) or carcinoma (Ca) were excluded. Patient age, gender, pathology report, available images, and a subset of histological slides were reviewed. Abnormal p53 IHC (p53+) was defined as nuclear staining in atypical glands exceeding the internal control basal squamous cells or the total absence of nuclear staining in glandular atypia. Cytoplasmic staining for rac in atypical glands was required for rac positivity (rac +). Follow up data were based on patients with subsequent esophageal biopsy specimens. Groups were compared using the Fisher exact test.
Results: The 224 patients (65 women) ranged in age from 33 to 94 years (mean = 64.1) and included 104 patients derived from the consultation practice of one of the authors (RP). Eighty-four patients were p53+ including 31 that were also rac +. Thirty five patients were rac + with 4 showing rac + alone. Twenty five additional patients showed rac staining in benign glands. This was interpreted as negative. Follow up was available in 60 patients (1-26 mos, mean = 9.2 mos) including 23 p53-/rac-, 21 p53+/rac-, 15 p53+/rac+ and 1 p53-/rac+. Seven (33.3%) p53+/rac- patients and 12 (80%) p53+/rac + progressed to HGD/Ca versus 1 (4.3%) with negative IHC (p = 0.019 and < 0.0001 respectively). In contrast 18 of 23 (78.3%) negative IHC patients remained negative for dysplasia versus 5 (23.8%) in the p53+/rac- group and 0 in the p53+/rac+ group (p = 0.0007 and < 0.0001 respectively). Follow up LGD/Ind was observed in 9 (42.8%) of the p53+/rac- patients, 3 (20%) of the p53+/rac+, and in 4 (17.4%) with negative IHC. Follow up on the 1 p53-/rac+ patient showed no dysplasia.
Conclusions: We conclude that a) p53 and rac IHC may be useful in stratifying patients with BE and glandular atypia into high-risk versus low-risk groups for progression to HGD/Ca; b) the combination p53+/rac+ defines a very high risk group for progression; and c) HGD/Ca occurs infrequently in patients without IHC abnormalities.
Monday, March 4, 2013 1:00 PM
Poster Session II # 109, Monday Afternoon