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Ulcerative colitis associated colon of the pathogenesis of colorectal cancer

Author: ZhengWeiYang
Tutor: QianJiaMing
School: Beijing Union Medical College
Course: Clinical
Keywords: ulcerative colits APC β-catenin wnt-1 p53 k-ras
CLC: R735.35
Type: PhD thesis
Year: 2009
Downloads: 30
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Abstract


Background Ulcerative colitis (UC) has been associated with a high risk of developing colorectal cancer (CRC). The CRC risk in UC increases with longer duration of colits, greater anatomic extent of colitis, the presence of primary sclerosing cholangitis, family history of CRC and so on. The neoplastic transformation in UC is thought to be different from the canonical adenoma-carcinoma sequence in sporadic CRC. Loss of APC function, considered to be a very common early event in sporadic CRC pathogenesis, is much less frequent and usually occurs late in the UC-associated dysplasia-carcinoma sequence. Conversely, p53mutations in sporadic CRC usually occur late in the adenoma-carcinoma sequence, whereas in patients with UC, p53mutation occur early and are often detected in mucosa that is non-dysplastic or indefinite for dysplasia. And there’s few studies focus on the roles of β-catenin and wnt-1in the pathogenesis of the UC-associated dysplasia-carcinoma sequence, which are key proteins in Wnt signal pathway. In our study, we try to search some clinical features of the UC-asscociated colorectal cancer from6cases, and make a research to see the roles of APC, β-catenin, P53, Wnt-1and k-ras played in the pathogenesis of the UC-associated colorectal cancer.Objective We try to make a mini-summary of the clinical features of the UC-asscociated colorectal cancer and give some clue on how to diagnose this disease and deal with these patients. And we try to make a research to determine the expression of APC, β-catenin, P53, Wnt-1and the mutation of k-ras in UC-associated colorectal cancer, UC, colorectal cancer and adenoma, and search the difference between UC-associated colorectal cancer and CRC in their pathogenesis.Methods and materials We summarized the clinical features, pathology, treatment, prognosis et. al of UC-associated colorectal cancer via analyzing6clinical cases from PUMCH. Thirty-four cases of UC, including6cases of UC-associated colorectal cancer, were studied in the research with16colectomy specimens and18colon endoscopy biopsy specimens, and fifteen colectomy specimens with tubulovillous adenoma, twelve coloectomy specimens with sporadic CRC and6colon endoscopy biopsy specimens with normal mucosa, which were proved by pathology department, were also collected. We first divided them into four groups such as UC-associated colorectal cancer(6), UC(28), CRC(12) and tubulovillous adenoma(15), and then divide the specimens of UC and UC-associated colorectal cancer into3groups by the years of the colitis duration (0-7years=15,8-16years=14, more than16years=5). Immunohistochemistry(IHC) was performed to study the expression of the APC, β-catenin, P53and Wnt-1in the colon mucosa of the specimens, using the rabbit anti-human antibody of anti-Wnt-1(Abcom), anti-APC, anti-β-catenin and anti-p53(Santa Cruz) and the IHC kit(DAKO). Microdissection and PCR-sequecing were used to detect the mutation of k-ras in the specimens.Results The incidence of UC-associated colorectal cancer in PUMCH in-patients from1984-2008was lower than that of sporadic CRC. It suggested that female cases may be more than male ones in UC-associated colorectal cancer, with younger age of onset than sporadic CRC. The patients always suffered UC with long duration and great extent of colitis, and often detected carcinoma in recta. The pathology of the carcinoma always turned out to be adenocarcinoma with poor prognosis.The protein APC,β-catenin, P53and Wnt-1were positive stained in many specimens of the UC-associated colorectal cancer, UC, sporadic CRC and tubulovillous adenoma, and they were all negative in the normal mucosa of the colon. The expression levels of the p53and β-catenin had significant difference in UC-associated colorectal cancer, UC, CRC and tubulovillous adenoma, and the expression level of the p53was elevated when the years of the colitis duration increased. And there was no statistical difference of the APC and wnt-1in the four groups and the expression levels of APC,β-catenin and wnt-1had no correlation with the years of the duration. The k-ras mutation was detected only in four cases with three CRC cases and one UC-associated colorectal cancer. Conclusion The incidence of UC-associated colorectal cancer was lower than that of sporadic CRC, with higher ratio of female cases and younger age of onset than those in sporadic CRC. The patients always suffered UC with long duration and great extent of colitis, and often detected adenocarcinoma in recta, with poor prognosis. The proteins APC, β-catenin, P53and Wnt-1are overexpressed in UC, and the leves of p53increased by the years of duration. It confirms that UC is an risk factor of CRC, and the risk may elevate when the years of the colitis duration increase. It also suggests that the molecular mechanism of the neoplastic transformation in UC may have something to do with the Wnt signal pathway.

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CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Intestinal neoplasms > Colon tumor
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