IMPLICATION OF KI-67 IMMUNOHISTOCHEMISTRY FOR MANAGEMENT OF INTRAMUCOSAL NEOPLASIA IN BARRETT’S ESOPHAGUS

Aims Histological assessment of intramucosal neoplasia in Barrett’s esophagus is important for appropriate treatment. High-grade dysplasia, which is nearly identical to intramucosal non-invasive adenocarcinoma in Japan, and invasive adenocarcinoma are recommended to be treated immediately, although their histological criteria remain subjective and poor reproducibility has not been resolved. We aimed to clarify the potential of Ki-67 and p53 immunohistochemistry as an alternative method to conventional histological evaluation.

Methods We enrolled 39 superficial adenocarcinoma of Barrett’s esophagus (24 intramucosal and 15 submucosal cancers) in 38 cases, resected endoscopically or surgically and diagnosed by Japanese GI pathologists from 2013 to 2014 at our institution. Endoscopic and clinicopathological features were evaluated, and immunohistochemistry for Ki-67 and p53 was performed to each representative section. Ki-67 staining pattern was categorized into two groups: diffuse pattern (positive cells showed diffuse distribution including the surface epithelium) or localized pattern (positive cells were localized to the lower two-third of the crypts). p53 staining was categorized into two groups: normal (wild-type pattern) or abnormal (overexpressed or null pattern).

Results Ki-67 diffuse pattern was 67% (16/24) in intramucosal cancers, whereas 100% (15/15) in submucosal cancers. Intramucosal cancers with Ki-67 diffuse pattern showed higher frequencies of having poorly differentiated component and positive lymphovascular invasion than those with Ki-67 localized pattern (18.8% vs 0%; and 25.0% vs 0%). Abnormal expression of p53 was frequent in both groups (75% in localized pattern and 87.5% in diffuse pattern), that had no significant differences.

Conclusions Majority of intramucosal cancers had identical characteristics to submucosal cancers in terms of Ki-67 and p53 expression patterns. They may have invasive potential and need to be treated immediately, whereas those with Ki-67 localized pattern may have lower risk and observation can be considered. Ki-67 immunohistochemistry can be expected as an objective tool for management of intramucosal neoplasia in Barrett’s esophagus.