Evaluation of p53 Immunohistochemistry Staining Patterns in Barrett Esophagus With Low-Grade Dysplasia

p53 immunohistochemistry (IHC) may be a useful diagnostic adjunct in Barrett esophagus (BE) dysplasia assessment. This is especially true in distinguishing indefinite for dysplasia (IND) from low-grade dysplasia (LGD), a distinction fraught with difficulty. Most previous work has equated p53 “overexpression” with a “positive” result. However, both missense-mutant and wild-type (WT) p53 may be overexpressed, while truncating mutations/deletions may result in complete absence of p53 staining (the latter often misinterpreted as a “negative” result). We performed a “molecular-based” p53 assessment on a cohort of BE specimens with LGD to answer this fundamental question: what is the rate of abnormal p53 staining in LGD (reported rate 9%-89%)? The answer speaks to the negative-predictive value of a WT p53 IHC result and the timing of TP53 mutation in neoplastic progression. 45 BE samples from 35 patients were confirmed to have LGD by a GI pathologist. p53 IHC (clone DO-7) was assessed as WT (weak to moderate staining), missense (clonal areas of diffuse, strong staining), null (clonal areas of completely absent staining), or combo (some combination of the above). Median age at the first sample was 68 years; 32 patients were men. 6 patients had more than one LGD sample: 3 with concordant and 3 with discordant p53 results. 32 (71%) samples demonstrated LGD only; the remaining 13 demonstrated LGD with HGD and/or carcinoma. The overall rate of p53 abnormality was 87% (missense 51%, null 18%, combo 18%); in specimens with only LGD the rate was similar (overall abnormal 82%: missense 44%, null 16%, combo 22%). Most BE LGD cases demonstrate abnormal p53 IHC staining. As such, a WT result argues reasonably strongly against the presence of dysplasia. TP53 mutation would appear to coincide with the development of LGD, and may occur as multiple, independent mutational events.