Mutations of <i>p53</i> in Morphologically Non‐neoplastic Mucosa of Long‐standing Ulcerative Colitis

Takaku, Hideya; Ajioka, Yoichi; Watanabe, Hidenobu; Hashidate, Hideki; Yamada, Satoshi; Yokoyama, Junji; Kazama, Shinsuke; Suda, Takeyasu; Hatakeyama, Katsuyoshi

doi:10.1111/j.1349-7006.2001.tb01073.x

Cited by 12 publications

(11 citation statements)

References 27 publications

(43 reference statements)

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“…Weak p53 expression may observed in healthy colonic mucosa and this may be due to wild-type p53; the meaning of this is uncertain. On the other hand, strong diffuse staining is thought to be a marker of mutant p53 [11,12]. Mutation of the p53 gene is the last step in non-IBD CRC but it appears to occur earlier in the pathway of IBD-related CRC [1,13].…”

Section: Discussionmentioning

confidence: 97%

Expression of p53, VEGF, Microvessel Density, and Cyclin-D1 in Noncancerous Tissue of Inflammatory Bowel Disease

et al. 2008

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We aimed to evaluate the carcinogenesis risk in inflammatory bowel disease via p53 mutation and its relation with hyperproliferation (cyclin-D1) and angiogenesis (with vascular endothelial growth factor [VEGF] and microvessel density) and whether these events play important roles in pathogenesis of inflammatory bowel disease. Colonic tissue samples of 26 ulcerative colitis, 6 Crohn's disease, and 8 amoebic colitis patients as well as samples of 10 healthy controls were stained with p53, cyclin-D1, CD34, and VEGF monoclonal antibodies by immunohistochemistry and evaluated semiquantitatively. Expression of p53 was higher in ulcerative colitis than in the healthy control and amoebic colitis groups (4.15 +/- 2.07, 1.4 +/- 1.5, 1.3 +/- 1.5; P < 0.001). The Crohn's disease group had the highest p53 expression (4.6 +/- 1.6). The Crohn's disease, ulcerative colitis, and amoebic colitis groups all had higher VEGF expression than did the healthy controls (respectively, 4.3 +/- 1.2, 2.92 +/- 2.0, 2.3 +/- 1.5, 0.6 +/- 0.97; P < 0.001). Also, microvessel density was statistically higher in all three colitis groups than in healthy controls. Cyclin-D1 expression in all four groups was similar. The study showed that p53 mutation was present in nonneoplastic mucosa of inflammatory bowel disease patients. Detecting strong p53 overexpression with VEGF overexpression may help in differentiating inflammatory bowel disease from other colitis.

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Section: Discussionmentioning

confidence: 97%

Expression of p53, VEGF, Microvessel Density, and Cyclin-D1 in Noncancerous Tissue of Inflammatory Bowel Disease

et al. 2008

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“…Previous studies have shown that p53 is mutated in non-cancerous and pre-cancerous epithelial lesions of patients with chronic Ulcerative Colitis (UC) (9, 10, 38, 39). Studies performed on p53 +/+ vs. p53 −/− mice have shown that although the intermediate inflammatory index (i.e.…”

Section: Discussionmentioning

confidence: 99%

American Ginseng Suppresses Colitis through p53-Mediated Apoptosis of Inflammatory Cells

Jin

Hofseth

Cui

et al. 2010

Cancer Prevention Research

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Ulcerative colitis is a dynamic, chronic inflammatory condition associated with an increased colon cancer risk. Inflammatory cell apoptosis is a key mechanism regulating ulcerative colitis. American ginseng (AG) is a putative antioxidant that can suppress hyperactive immune cells. We have recently shown that AG can prevent and treat mouse colitis. Because p53 levels are elevated in inflammatory cells in both mouse and human colitis, we tested the hypothesis that AG protects from colitis by driving inflammatory cell apoptosis through a p53 mechanism. We used isogenic p53 +/+ and p53 are consistent with our in vitro data and with the hypothesis that AG drives inflammatory cell apoptosis in vivo, providing a mechanism by which AG protects from colitis in this DSS mouse model.

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“…Unlike in sporadic CRCs, IBD-associated cancer mutations and LOH in p53 are early events that can already be found in macroscopically normal looking mucosa [52][53][54] . In contrast, mutations in k-ras are relatively infrequent.…”

Section: Genetics Of Ulcerative Colitis Associated Colorectal Cancersmentioning

confidence: 99%

Risk for colorectal cancer in ulcerative colitis: Changes, causes and management strategies

Lakatos¹,

Lakatos²

2008

WJG

368

245

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Since the first report of an inflammatory bowel disease (IBD) case associated with colorectal cancer (CRC) by Crohn and Rosenberg [1] , significant efforts have been made to elucidate this presumed association. Nowadays, the association between IBD and the increased risk for CRC is widely accepted. Although CRC, complicating ulcerative colitis and Crohn's disease, accounts only for 1%-2% of all cases of CRC in the general population, it is considered a serious complication of the disease and accounts for approximately 10%-15% of all deaths in IBD patients [2] . The age at diagnosis of CRC associated with IBD is 15-20 years earlier compared to sporadic cancers. In the meta-analysis by Eaden et al [3] , the average age at diagnosis was 43.2 years. Similarly, in a recent publication from Eastern Europe [4] , it was found to be 50.9 years, 10-15 years younger compared to sporadic CRC cases from the same area (62.2 years) [5] . According to US [6] and Canadian [7] publications, almost two-thirds of the affected patients were males, yet results are conflicting [4,8] . In addition, the frequency of multiple CRCs is higher than in patients with sporadic CRC [9] .The increased risk of CRC in UC is almost a universal finding [3,[10][11][12][13] , yet the extent of this risk varies considerably with differences in study design and geographic area. The initial reports were published by tertiary gastroenterology centers, thus the high risk detected might have been a consequence of referral bias and overinterpretation due to the high percentage of extensive and chronically active cases in these cohorts. Results of population-based studies are more reliable; however, several geographical and ethnic differences have been noted.The report of the meta-analysis by Eaden et al [3] in 2001 was one of several milestones in this subject. The incidence of UC-associated CRC was estimated based on 116 articles involving 54 478 patients in whom 1698 CRC cases were detected. This was a mixture of referral center-based, hospital-based, and population-based studies of variable methodological qualities and levels of detail. The reported incidence was higher in the US AbstractThe risk of colorectal cancer for any patient with ulcerative colitis is known to be elevated, and is estimated to be 2% after 10 years, 8% after 20 years and 18% after 30 years of disease. Risk factors for cancer include extent and duration of ulcerative colitis, primary sclerosing cholangitis, a family history of sporadic colorectal cancer, severity of histologic bowel inflammation, and in some studies, young age at onset of colitis. In this review, the authors discuss recent epidemiological trends and causes for the observed changes. Population-based studies published within the past 5 years suggest that this risk has decreased over time, despite the low frequency of colectomies. The crude annual incidence rate of colorectal cancer in ulcerative colitis ranges from approximately 0.06% to 0.16% with a relative risk of 1.0-2.75. The exact mechanism for this chang...

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

Cited by 12 publications

References 27 publications

Expression of p53, VEGF, Microvessel Density, and Cyclin-D1 in Noncancerous Tissue of Inflammatory Bowel Disease

Expression of p53, VEGF, Microvessel Density, and Cyclin-D1 in Noncancerous Tissue of Inflammatory Bowel Disease

American Ginseng Suppresses Colitis through p53-Mediated Apoptosis of Inflammatory Cells

Risk for colorectal cancer in ulcerative colitis: Changes, causes and management strategies

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