Diagnostic Utility of p53 and Cytokeratin 7 Immunohistochemistry in Idiopathic Inflammatory Bowel Disease-Associated Neoplasia
Hao Xie, Shu-Yuan Xiao, Rish Pai, Keith Lai, Yinghong Wang, Bo Shen, Xiuli Liu. Cleveland Clinic, Cleveland, OH; University of Chicago, Chicago, IL
Background: Long-standing inflammatory bowel disease (IBD) is associated with increased risk of developing colorectal adenocarcinoma. Significant intra- and inter-observers' variability exists in histologic interpretation of dysplasia in surveillance biopsies. The aim of this study is to evaluate the utility of a panel of immunohistochemical markers in diagnosing IBD-associated neoplasia.
Design: We reviewed 39 colectomy specimens with IBD-associated neoplasia. In these 39 cases, we identified 172 foci of interest (5 normal, 58 negative for dysplasia, 15 indefinite for dysplasia, 59 low-grade dysplasia, 18 high-grade dysplasia, and 17 invasive adenocarcinoma). They were subjected to immunohistochemistry for p53 and cytokeratin 7 (CK7). Logistic regression was used to evaluate their association with the presence of dysplasia. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoffs and assess the diagnostic performance of p53 and CK7.
Results: Both p53 nuclear staining and CK7 immunoreactivity gradually increased in the progression of IBD-associated neoplasia (P < 0.0001). CK7 immunoreactivity increased along with an increase in inflammation severity (P = 0.0002) as well as reactive changes (P = 0.04) in the colonic mucosa. But p53 nuclear staining was independent of either feature. When both p53 > 8% and CK7 > 30% as identified from logistic regression and ROC curves were used to diagnose dysplasia, the specificity achieved was 95%. When either p53 > 8% or CK7 > 30% was used to diagnose dysplasia, the sensitivity achieved was 82% (Table 1).
|p53>8% and CK7>30%||N/A||36%||95%||0.88||0.58||N/A|
|p53>8% or CK7>30%||N/A||82%||56%||0.66||0.75||N/A|