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 p53 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.
Takaku
H
H
First Department of Pathology, Niigata University School of Medicine, Niigata 951-8510, Japan. htkq@qg7.so-net.ne.jp
Ajioka
Y
Y
Watanabe
H
H
Hashidate
H
H
Yamada
S
S
Yokoyama
J
J
Kazama
S
S
Suda
T
T
Hatakeyama
K
K
D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000276:immunology
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53