Expression Profile of p53 and p21 in Large Bowel Mucosa as Biomarkers of Inflammatory-Related Carcinogenesis in Ulcerative Colitis

Abstract

Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease that slightly increases the risk of colorectal cancer in patients with long-standing extended disease. Overexpression of p53 and p21 in colonic epithelia is usually detected in UC patients when no dysplasia is histologically seen and it is used by pathologists as a discriminator between regenerative changes and intraepithelial neoplasia, as well as a tissue biomarker useful to predict the risk of evolution toward malignancy. We present a one-year prospective observational study including a cohort of 45 patients with UC; p53 and p21 were evaluated in epithelial cells. p53 was positive in 74 samples revealed in 5% to 90% of epithelial cells, while 63 biopsies had strong positivity for p21 in 5% to 50% of epithelial cells. Architectural distortion was significantly correlated with p53 overexpression in epithelial cells. Thus, we consider that architectural distortion is a good substitute for p53 and p21 expression. We recommend use of p53 as the most valuable tissue biomarker in surveillance of UC patients, identifying the patients with higher risk for dysplasia. Association of p21 is also recommended for a better quantification of risk and for diminishing the false-negative results.

Morphological Classification of Corrupted Colonic Crypts in Ulcerative Colitis

“…This notion is validated by recent findings by Popp et al (34) showing that p53 overexpression (a biomarker of epithelial carcinogenesis) significantly correlated with architectural distortions of the crypts in UC (34). The results of Popp et al (34) seem to be in concert with the our findings, inasmuch as HGD in UC was mainly found in CCC.…”

Systematic Classification of Colonic Crypts with Architectural Distortions Inulcerative Colitis

“…The authors found that architectural distortion significantly correlated with p53 over expression [34].The results of Popp et al [34]seem to be in concert with the present findings,inasmuch as HGD in UC mainly occurred in crypts with architectural distortions (here referred to as CAD).…”

“…This notion is validated by recent findings showing that p53 over expression (a biomarker of epithelial carcinogenesis) significantly correlated with architectural distortions of the crypts in UC [34] …”

“…In a recent work, Popp et al [34] found over expression of p53 -a tissue biomarker of epithelial carcinogenesis-in sections of UC patients. The authors found that architectural distortion significantly correlated with p53 over expression [34].The results of Popp et al [34]seem to be in concert with the present findings,inasmuch as HGD in UC mainly occurred in crypts with architectural distortions (here referred to as CAD).…”

Histologic Features with Predictive Value for Outcome of Patients with Ulcerative Colitis

“…Some immunohistochemical markers, such as p53, p21, bcl-2, AMACR (alpha methyl-CoA racemase), can be used to sustain a morphologic diagnosis of dysplasia [1,29]. Considering that treatment for UC-associated dysplasia is usually colectomy and there is a poor inter-and intraobserver agreement, especially for the diagnosis of LGD, it is mandatory that the diagnosis is confirmed by an independent expert pathologist before any invasive therapy [34][35][36].…”