Mutations of p53 in Morphologically Non‐neoplastic Mucosa of Long‐standing Ulcerative Colitis

Two cases of ulcerative colitis (UC)‐associated carcinoma or dysplasia and morphologically non‐neoplastic mucosa with p53 protein overexpression (MNNM‐p53OE) were selected. DNA was extracted from the paraffin blocks of these lesions and exons 5‐8 of the p53 gene were analyzed by PCR and direct sequencing. In addition, mutations in K‐ras codon 12 were analyzed by PCR‐RFLP methods. MNNM‐p53OE was located surrounding and adjoining a coexisting carcinoma and/or dysplasia. A p53 mutation was detected in 12/22 (54.5%) MNNM‐p53OE samples, 4/8 (50%) dysplasia samples and 8/8 (100%) carcinoma samples. The/j53 mutations detected in MNNM‐p53OE were identical to those demonstrated in the adjoining carcinoma and/or dysplasia. No K‐ras codon 12 mutation was detected in any of the samples. These results indicate that MNNM‐p53OE may share an identical clonal linkage with a coexisting carcinoma and/or dysplasia, and may be an initial and submorphological form of UC‐associated neoplasia. Recognition of MNNM‐p53OE in biopsy specimens may help to identify patients with UC at risk of developing colorectal carcinoma.