Evaluation of the usefulness of testing for p53 mutations in colorectal cancer surveillance for ulcerative colitis

Abstract

p53 Mutations 1) are associated with, and likely precede, dysplasia and cancer, 2) are associated with cancer-related mortality, and 3) may possibly be prevented by folic acid supplementation.

Ulcerative Colitis-Associated Colorectal Cancer is Frequently Associated with the Microsatellite Instability Pathway

“…8 Novel techniques for detection of high-risk individuals are needed to optimize surveillance strategies and decrease risk of CRC development. 4,11 In this study, there was a correlation between histologic findings and high-MSI. An MSI analysis of biopsy specimens may help differentiate colitic neoplasms from inflammatory changes and might provide more reliable information on the probability of future malignancy.…”

“…Although a random biopsy for p53 immunohistochemical assessment has been used to aid diagnosis of dysplasia or cancer, early detection of UC-ACRC still is difficult. 4 Sporadic CRC are widely considered to result from the sequential accumulation of alterations in genes that regulate the growth of colonic epithelial cells. 5 UC-ACRC is believed to occur by a progression from a nonneoplastic inflammatory epithelium to dysplasia to carcinoma and develop as a consequence of sequential episodes of somatic genetic mutation.…”

“…The elucidation of the molecular mechanisms of colonic carcinogenesis may provide a reliable molecular marker predicting the probability of future malignancy. 4,11 In this study, genetic alterations of the epithelium in UC were investigated to clarify the molecular mechanism for the carcinogenesis of UC-ACRC.…”

“…3 +, band shift positive; −, band shift negative. 4 Target gene, target gene mutation; TGF, TGFβRII; MB, MBD4; h3, hMSH3; h6, hMSH6 indicate mutation positive. 5 LOH, loss of heterozygosity; Ho, homozygous; Shift, microsatellite instability; NI, not informative.…”

Efficacy of surveillance and molecular markers for detection of ulcerative colitis-associated colorectal neoplasia

“…Several studies have reported p53 alterations occurring in nonneoplastic epithelium from patients with longstanding and extensive UC. Lashner et al 38 examined p53 alterations in 95 patients with longstanding and extensive UC using immunohistochemical methods, and showed that patients displaying p53 alterations in nonneoplastic epithelium were significantly more likely to develop neoplasia. Similarly, Holzmann et al 34 reported that p53 mutations in nonneoplastic epithelium were significantly more frequent in patients with neoplasia than in those without neoplasia.…”