Diagnostic utility of TP53 and cytokeratin 7 immunohistochemistry in idiopathic inflammatory bowel disease-associated neoplasia

Abstract

Long-standing inflammatory bowel disease is associated with increased risk of developing colorectal adenocarcinoma. Significant intra-and inter-observers' variability exists in histologic interpretation of dysplasia in surveillance biopsies. In this study, we evaluated the utility of a panel of immunohistochemical markers in diagnosing inflammatory bowel disease-associated neoplasia. We reviewed 39 colectomy specimens with inflammatory bowel disease-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 highgrade dysplasia, and 17 invasive adenocarcinoma). They were subjected to immunohistochemistry for TP53 and CK7. Logistic regression was used to evaluate their association with the presence of dysplasia. Receiver operating characteristic curves were used to determine the optimal cutoffs and assess the diagnostic performance of TP53 and CK7. Both TP53 nuclear staining and CK7 immunoreactivity gradually increased in the progression of inflammatory bowel disease-associated neoplasia (Po0.0001). CK7 immunoreactivity increased along with the increase of inflammation severity (P ¼ 0.0002) as well as reactive changes (P ¼ 0.04) in the colonic mucosa. But TP53 nuclear staining was independent of either feature. When both TP5348% and CK7430% as identified from logistic regression and receiver operating characteristic curves were used to diagnose dysplasia, the specificity achieved as high as 95%. When either TP5348% or CK7430% was used to diagnose dysplasia, the sensitivity achieved was 82%. Our results suggested that a combination of CK7 and TP53 immunohistochemistry may be helpful in diagnosing inflammatory bowel disease-associated dysplasia in difficult cases.

Overexpression of p53 predicts colorectal neoplasia risk in patients with inflammatory bowel disease and mucosa changes indefinite for dysplasia

“…We performed immunohistochemistry for p53 and cytokeratin 7 in 44 cases of colon biopsies with IBD-IND and investigated the value of these two markers in predicting neoplastic progression in IBD-IND because our previous study showed overexpression of p53 and cytokeratin 7 in IBD-associated neoplasia in a partially overlapping and partially complementary fashion [ 17 ]. In our current cohort of IBD patients with IND, 27% of cases had ≥ 5% epithelial nuclei with intense p53 expression; this rate is comparable with the results of a previous study that found 21% of colon biopsies with IND showed intense nuclear p53 immunoreactivity in ≥ 5% epithelial nuclei [ 19 ].…”

“…We have previously shown that IBD patients with IND mucosal changes carried significant risk for progression to neoplasia: 25.2% of patients with IBD-IND developed dysplasia or carcinoma during a mean follow-up of 98.6 months, with an incidence of all neoplasia at 3.2 cases/100 person-years and an incidence of advanced neoplasia at 1.5 cases/100 person-years [ 14 ]. We also reported the diagnostic utility of p53 and cytokeratin 7 in IBD-associated neoplasia [ 17 ]. This study aimed to determine the predictive value of the two markers for neoplasia progression risk in an IBD-IND population.…”

Expression of p53 predicts risk of prevalent and incident advanced neoplasia in patients with Barrett's esophagus and epithelial changes indefinite for dysplasia

“…Epithelial changes were classified as negative for dysplasia, positive for dysplasia (LGD, HGD, or EAC) or IND. Immunohistochemical staining for p53, AMACR, and cyclin D1 was performed on whole tissue sections from Hollande's fixed or formalin-fixed and paraffin-embedded tissue, as described previously [19]. In brief, de-paraffinized tissue sections were stained with antibodies against p53 (clone DO-7, at a 1:20 working dilution; Dako Corp., Carpinteria, CA, USA), AMACR (clone 13H4, at a 1:100 working dilution, Zeta Corp., Sierra Madre, CA, USA), and cyclin D1 (clone SP4, at a 1:100 working dilution; ThermoLabVision, Waltham, MA, USA).…”

“…who was blinded to the neoplasia outcomes. The expression of p53 was determined as the percentage of epithelial cells in the esophageal columnar tissue showing nuclear staining within a high-power field [19] (Figure 1A). High p53 expression was defined as more than 5% of the epithelial cells in the esophageal columnar tissue showing nuclear staining.…”

Classification and diagnosis of colorectal dysplasia in inflammatory bowel disease

“…23 Despite the promising findings, the diagnostic utility of CK7 is limited due to frequent reactivity to nondysplastic epithelium (31% of cases) and therefore should not be used as a stand-alone marker. 23 …”