title: 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 high-grade 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 (P<0.0001). CK7 immunoreactivity increased along with the increase of inflammation severity (P=0.0002) as well as reactive changes (P=0.04) in the colonic mucosa. But TP53 nuclear staining was independent of either feature. When both TP53>8% and CK7>30% as identified from logistic regression and receiver operating characteristic curves were used to diagnose dysplasia, the specificity achieved as high as 95%. When either TP53>8% or CK7>30% 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.
authors.affiliation: 1] Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA [2] Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL, USA.
authors.forename: Shu-Yuan
authors.initials: SY
authors.lastname: Xiao
authors.affiliation: Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Rish
authors.initials: R
authors.lastname: Pai
authors.affiliation: Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Shadrach
authors.affiliation: Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Carver
authors.affiliation: Department of Gastroenterology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Weixun
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000150:complications; D053552:Keratin-7 / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism; D012372:ROC Curve; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D055815:Young Adult
chemical_list: D053552:Keratin-7; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53