Mutations in the p53 gene: An early marker of neoplastic progression in ulcerative colitis

Brentnall, Teresa A.; Crispin, David A.; Rabinovitch, Peter S.; Haggitt, Rodger C.; Rubin, Cyrus E.; Stevens, Alexander R.; Burmer, Glenna C.

doi:10.1016/0016-5085(94)90161-9

Cited by 380 publications

(225 citation statements)

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“…At a molecular level, p53 gene mutations or p53 protein overexpression, which is a late event in the development of sporadic colorectal carcinoma, have been commonly reported as early events in the dysplasia-carcinoma sequences in UC-associated carcinomas. [11][12][13][14] These results provide evidence that UC-associated cancer may develop along a pathway that is different from that of sporadic colorectal cancer.…”

mentioning

confidence: 76%

Predominant T helper type 2‐inflammatory responses promote murine colon cancers

Osawa

Nakajima

Fujisawa

et al. 2005

Intl Journal of Cancer

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Colon cancer is one of the most serious complications of inflammatory bowel diseases, especially ulcerative colitis (UC). Previous studies have shown that characteristic immunological event during inflammation in UC is the expression of T helper-type 2 (Th2) cell-derived cytokines. In this study, we investigated the influence of a predominant Th2-type cytokine response in colitis on carcinogen-induced colon tumors. Wild type (WT), interferon gamma (IFN-c) gene deficient (2/2) [Th2 dominant] or interleukin (IL)-4 2/2 [Th1-dominant] mice of BALB/c background were used in this study. To compare tumor formation, mice were given the carcinogen azoxymethane (AOM) and intrarectal administration of trinitrobenzene sulfonic acid (TNBS), to induce colitis. Thirtythree weeks after initial treatment, the total colon was examined. When IFN-c 2/2 mice were treated with AOM and TNBS, significantly higher number of tumors were seen (8.4 6 1.7) than in WT (3.3 6 2.9) or IL-4 2/2 (3.1 6 3.4) mice, which received identical treatments. A separate set of experiment, using less doses of AOM and TNBS also showed the higher frequency of tumor formation in IFN-c 2/2 mice than in IL-4 2/2 mice. Histologically, the tumors were well-or moderately-differentiated adenocarcinomas. No invasion into the submucosal or serosal layers of the intestine was seen. In immunohistological staining, some tumors in IFN-c 2/2 mice showed distinct nuclear expression of b-catenin, in contrast to the strong membrane staining seen in tumors of IL-4 2/2 mice. In conclusion, colonic inflammation associated with Th2-donimant cytokine responses enhanced the formation of malignant neoplasms. ' 2005 Wiley-Liss, Inc.

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mentioning

confidence: 76%

Predominant T helper type 2‐inflammatory responses promote murine colon cancers

Osawa

Nakajima

Fujisawa

et al. 2005

Intl Journal of Cancer

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“…© 2008 American Association for Cancer clincancerres.aacrjournals.org Downloaded from common methodology to observe ACF. Regarding the genetic abnormality of ACF, we found a highly frequent K-ras mutation and GSTP1-1 overexpression and also showed that GSTP1-1 endows ACF with resistance to bile salt -induced apoptosis (11 -13).With regard to the genetic abnormality of colitis-associated cancer and dysplasia, mutations of K-ras and APC are relatively rare (14 -17), and in contrast, p53 mutation is frequently positive (16,18,19). Moreover, hypermethylation of genes such as the p16 gene has recently been detected (20,21).…”

mentioning

confidence: 83%

“…It has been reported that p53 mutations are frequently detected in dysplasia and cancer tissues from patients with UC (16,18,19). Therefore, we investigated for p53 mutations in the hotspot region (exons 5-9) employing nonradioisotopic single-strand conformation polymorphism in 11 colitis ACF and 5 dysplasia specimens from patients with UC.…”

Section: Endoscopic and Histologic Features Of Dysplasia (A-c) Acfmentioning

confidence: 99%

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Aberrant Crypt Foci as Precursors of the Dysplasia-Carcinoma Sequence in Patients with Ulcerative Colitis

Kukitsu¹,

Takayama²,

Miyanishi³

et al. 2008

Clinical Cancer Research

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Purpose: Long-standing ulcerative colitis (UC) predisposes patients to the development of colorectal cancer, but surveillance of colitis-associated cancer by detecting the precancerous lesion dysplasia is often difficult because of its rare occurrence and normal-looking appearance. In sporadic colorectal cancer, aberrant crypt foci (ACF) have been reported by many investigators to be precursor lesions of the adenoma-carcinoma sequence. In the present study, we analyzed the genetic background of ACF to determine whether they could be precursors for dysplasia, and we examined the usefulness of endoscopic examination of ACF as a surrogate marker for surveillance of colitis-associated cancer. Experimental Design: ACF were examined in 28 UC patients (19 patients with UC alone and 9 patients with UC and dysplasia; 2 of those patients with dysplasia also had cancer) using magnifying endoscopy. K-ras, APC, and p53 mutations were analyzed by two-step PCR RFLP, in vitro^synthesized protein assay, and single-strand conformation polymorphism, respectively. Methylation of p16 was analyzed by methylation-specific PCR. Results: ACF that appeared distinct endoscopically and histologically were identified in 27 out of 28 UC patients. They were negative for K-ras, APC, and p53 mutations but were frequently positive for p16 methylation (8 of 11; 73%). In dysplasia, K-ras and APC mutations were negative but p53 mutation (3 of 5; 60%) and p16 methylation (3 of 5; 60%) were positive. There was a significant stepwise increase in the number of ACF from patients with UC alone to patients with dysplasia and to patients with cancer. Univariate and multivariate analyses showed significant correlations between ACF and dysplasia. Conclusions: We have disclosed an ACF-dysplasia-cancer sequence in colitis-associated carcinogenesis similar to the ACF-adenoma-carcinoma sequence in sporadic colon carcinogenesis. This study suggests the use of ACF instead of dysplasia for the surveillance of colitis cancer and warrants further evaluation of ACF as a surveillance marker in large-scale studies.It is commonly recognized that long-standing ulcerative colitis (UC) predisposes patients to the development of colorectal cancer (1). However, the detection of early colorectal cancer is often difficult in patients with UC because there is inflammation in the background mucosa and it predominantly represents flat-type ill-delineated lesions (2, 3). Therefore, colitis-associated cancer is often detected at an advanced stage and is characterized by a very poor prognosis. One approach to overcome this difficulty is to use dysplasia, which is considered to be a precancerous lesion in colitis-associated cancer, as a surrogate marker for early detection of colitis-associated cancer (4, 5). However, identification of dysplasia by endoscopy requires greater skill than detection of cancer itself because of its rare occurrence and apparently normal-looking appearance (6).We previously succeeded in identifying aberrant crypt foci (ACF) in non-UC subjects using ...

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“…Biologically different in colorectal cancer which depends on life style variables and geographic differences could possibly answer why frequency of APC1A methylation differ in our population compared with Herman's study. Studies showed that p53 mutations occur early and are more frequent in non-dysplastic mucosa in ulcerative colitis associated neoplasia (Burmer et al, 1992;Yin et al, 1993;Brentnall et al, 1994). Interestingly, APC2 were associated in interaction with the P53/Bcl2 in cell cycle progression and cell death pathway (Nakagawa et al, 2000).…”

Section: Mgmt-b Gene Promoter Hypermethylation In Patients With Inflamentioning

confidence: 99%

MGMT-B Gene Promoter Hypermethylation in Patients with Inflammatory Bowel Disease - A Novel Finding

Mokarram

Kavousipour²,

Sarabi³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Mutations in the p53 gene: An early marker of neoplastic progression in ulcerative colitis

Cited by 380 publications

References 20 publications

Predominant T helper type 2‐inflammatory responses promote murine colon cancers

Predominant T helper type 2‐inflammatory responses promote murine colon cancers

Aberrant Crypt Foci as Precursors of the Dysplasia-Carcinoma Sequence in Patients with Ulcerative Colitis

MGMT-B Gene Promoter Hypermethylation in Patients with Inflammatory Bowel Disease - A Novel Finding

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