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Recognition of the p53 Null Staining Pattern Increases the Detection of p53 Alterations in Inflammatory Bowel Disease-Associated Carcinomas Jeremy S. Ditelberg, MD, Shelley Karl, BS, Mark Redston, MD Miraca Life Sciences Research Institute, Newton, Massachusetts Background Results Colorectal cancer (CRC) occurring in the setting of Inflammatory Biopsies from 917,599 colonoscopies were interpreted on 878,835 Bowel Disease (IBD) is relatively uncommon. Mutations in p53 patients (51% female, 49% male) during the study period. Of have been found in these cancers, and have been proposed these, 16,631 unique patients (48% female, 52% male) had as a possible genetic marker with utility in detection of these histological and clinical features of UC while 5,736 patients had cancers and their precursor dysplasias. We undertook this study histological and clinical features of CD. During this period, 6,211 to determine the frequency of p53 null alterations, a recently CRCs were diagnosed (52% male, 48% female). Of these cancers, observed pattern that has not previously been described in 22 occurred in patients with UC (prevalence of 22/16,631 = colitis-associated neoplasia. 0.13%), and 5 occurred in patients with CD (prevalence of 5/5,736 = 0.09%). 19 IBD patients were male (70.4%) and 8 were female Methods Patients with CRC were selected from the pathology database of Miraca Life Sciences. The database includes demographic and clinical information, summary of the endoscopic report, biopsy location, and the histopathologic report for each biopsy specimen. Cases of CRC with a report date from 11/1/2007 to 11/30/2011 were extracted from the database. From these cases, a database search was performed to extract patients with a history of Ulcerative Colitis (UC) and Crohn Disease (CD). p53 immunohistochemical staining was performed on the carcinomas and interpreted as wild-type (<20% 2-3+ nuclear positivity), (29.6%). The mean age was 58 years (median 56 years, standard deviation 13.5 years, range 33 to 84 years). Of these tumors, 14 Figure 1. Wild-type staining pattern. The tumor cell nuclei show variable staining intensity. Conclusions • The p53 null staining pattern is very common in colitisassociated carcinoma, and more than doubles the detectable frequency of p53 immunohistochemical alterations in these tumors. • This finding indicates that p53 alterations are one of the most common genetic abnormalities in colitis-associated neoplasia, Figure 2. Mutant staining pattern. The tumor cell nuclei show strong, uniform staining. (51.9%) were moderately differentiated (MD) and 13 (48.1%) were and has important implications for the potential use of p53 in screening and early detection programs. • CRC occurring in the setting of IBD is rare, occurs predominantly in males and tends to be poorly differentiated. poorly differentiated (PD). Immunohistochemical staining for p53 References showed abnormalities in 24/27 (89%), including 14 carcinomas 1.Shivakumar BM, et al. Molecular alterations in colitis-associated with null pattern (51.9%), 10 with mutant pattern (37.0%) and 3 with wild-type pattern (11.1%). One MD carcinoma and 2 PD carcinomas showed wild-type p53 staining. Figure 3. Null staining pattern. The tumor cell nuclei show no staining. Note background stromal cells which show wildtype staining. colorectal neoplasia: study from a low prevalence area using magnifying chromo colonoscopy. J Crohns Colitis. 2012 Jul;6(6):647-54. 2.Fujii S, et al. Usefulness of analysis of p53 alteration and observation of surface microstructure for diagnosis of ulcerative colitis-associated colorectal neoplasia. J Exp Clin Cancer Res. 2003 Mar;22(1):107-15. 3.Yoshida T, et al. Diverse p53 alterations in ulcerative colitis-associated point mutant (>50% 2-3+ nuclear positivity) or null (no nuclear low-grade dysplasia: full-length gene sequencing in microdissected positivity). single crypts. J Pathol. 2003 Feb;199(2):166-75.