Download Figure 1. Wild-type staining pattern. The tumor cell nuclei show

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
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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.
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