MDM2/p53 protein expression in the development of colorectal adenocarcinoma,

Abdel-Fattah, Ghada; Yoffe, Boris; Krishnan, Bhuvaneswari; Khaoustov, Vladimir I.; Itani, Kamal M.F.

doi:10.1016/s1091-255x(00)80041-4

Cited by 37 publications

(22 citation statements)

References 25 publications

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“…The latter finding is in line with previous reports [7,8,[39][40][41]. Importantly, we could not find any association between mdm2 expression and clinico-pathological parameters; this is a consistent feature of other studies [7,8,41], further reinforcing the suggestion that mdm2 might play a significant role in a very early stage of colorectal carcinogenesis.…”

Section: Discussionsupporting

confidence: 93%

Potential Role of Apoptosis and Apoptotic Regulatory Proteins in Colorectal Neoplasia: Correlations with Clinico-Pathological Parameters and Survival

Tzouvala¹,

Lazaris

Papatheodoridis³

et al. 2007

Dig Dis Sci

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An imbalance between apoptotic and proliferative processes is believed to underlie colorectal neoplasia. We evaluated the expression of bcl-2, p53, mdm2 proteins, and apoptosis in colorectal neoplasms, as well as their correlation with clinico-pathological parameters, using image analysis. Biopsies from 46 colorectal cancers, 121 adenomas, and 25 controls were studied using monoclonal antibodies against p53, bcl-2, mdm2 and the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) method for apoptosis. P53 and bcl2 protein expression was higher in adenomas >or=1 cm (P < 0.03) and tubulovillous-villous adenomas (P < 0.03), and correlated with dysplasia (P < 0.03). In Cox regression analysis, Dukes' stage was the most significant independent prognostic indicator of a worse survival (P < 0.019), whereas when stage was eliminated, bcl-2 expression was also a powerful predictor for bad prognosis (P = 0.02). In conclusion, both bcl-2 and p53 immunohistochemical profiles may be useful adjuncts in detecting adenomas with a malignant potential, whereas bcl-2 could be used in combination with Dukes' stage as a predictor of prognosis in colorectal cancer.

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Section: Discussionsupporting

confidence: 93%

Potential Role of Apoptosis and Apoptotic Regulatory Proteins in Colorectal Neoplasia: Correlations with Clinico-Pathological Parameters and Survival

Tzouvala¹,

Lazaris

Papatheodoridis³

et al. 2007

Dig Dis Sci

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“…In our study, the incidence of mdm2-positive tumours was 30% which is nearly the same rate reported by other authors [25, 26, 27, 28]. We could not find any association between the main clinical and histopathological tumour features and mdm2 expression.…”

Section: Discussionsupporting

confidence: 89%

mdm2-p53 Interaction: Lack of Correlation with the Response to 5-Fluorouracil in Advanced Colorectal Cancer

Paradiso¹,

Ranieri

Simone

et al. 2002

Oncology

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Objective: We investigated the relevance of mdm2 and p53 primary tumour expression to the clinical outcome of a consecutive series of advanced colorectal cancer patients treated with a 5-fluorouracil-based chemotherapy. Methods: The expression of p53 and mdm2 was analyzed by an immunohistochemical assay in 80 formalin-fixed paraffin embedded primary tumour samples and related to the clinical response to 5-fluorouracil therapy and to the prognosis of the patients. In a subgroup of 46 tumours, the apoptotic index (AI) as determined by the Tunel technique was also assessed. Results: Nuclear immunostaining of p53 and mdm2 was present in 42 and 30% of the cases, respectively. No correlation was demonstrated between p53 and mdm2 expression (rs = –0.01; p > 0.05). With regard to the clinical outcome, no statistical association was demonstrated among p53 and mdm2 expression, AI, probability of clinical response to treatment, time to progression, or overall survival. The subgroup of patients with a p53-negative/mdm2-positive tumour showed a worse response rate (15%); however, mdm2-positive/AI-negative tumours showed a 0% (0/7) probability of a clinical response as compared with 30% (9/30) of the remaining tumour patient subgroups; this also translated in a significantly worse overall survival probability (p = 0.01 by log rank). Conclusions: The analysis of mdm2 expression does not add significant clinical information in colorectal cancers with a different p53 status. Conversely, further analysis of AI seems to give data of a promising prognostic-predictive value.

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“…Recent studies focused on Mdm2 expression in human epithelial neoplasms. A similar result has been reported in colorectal adenocarcinoma, Mdm2 expression was detected in both adenomas and adenocarcinomas and associated with negative p53 expression [1]. Our recent study has suggested that increased Mdm2 expression is an early event in canine cir- Table 1 cumanal gland tumorigenesis, and its expression decreased in adenocarcinomas [24].…”

Section: Discussionsupporting

confidence: 84%

“…A reciprocal relationship between the presence of a p53 mutation and Mdm2 gene amplification was demonstrated in canine soft-tissue sarcomas [25]. By contrast, Mdm2 overexpression has been shown to be associated with negative p53 expression [1]. Mdm2 overexpression was present in feline mammary gland adenomas in the absence of p53 overexpression.…”

Section: Discussionmentioning

confidence: 96%

Immunohistochemical Detection of Mdm2 and p53 in Feline Mammary Gland Tumors

Nakano

Taura

2006

The Journal of Veterinary Medical Science

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ABSTRACT. The objective of this study was to evaluate nuclear reactivity of Mdm2 and p53 proteins by immunohistochemical means in feline mammary gland tumors; 12 adenomas which included 6 adenomatous lesions obtained from the tissue adjacent to adenocarcinomas, and 22 adenocarcinomas. Seven adenomas and 18 adenocarcinomas showed moderate or marked Mdm2 reactivity. Sixteen adenocarcinomas showed moderate to marked p53 reactivity, but 9 adenomas showed none. Discordant Mdm2 overexpression was found in 5 adenomas and 3 adenocarcinomas, although co-overexpression of Mdm2 and p53 was found in 15 adenocarcinomas. These results suggest that nuclear overexpression of Mdm2 is present in the tumors of early stage without p53 overexpression and related to feline mammary gland tumorigenesis. Nuclear overexpression of p53 is more frequent in adenocarcinomas, but not in adenomas. KEY WORDS: feline mammary tumor, Mdm2, p53.J. Vet. Med. Sci. 68(5): 421-425, 2006 Mammary neoplasm is the third most common tumor, following lymphoid and cutaneous neoplasms in cats and simple type adenocarcinoma, and complex type tumor and myoepithelioma are found rarely [12]. The molecular and genetic events contributing to feline mammary gland tumorigenesis are largely unknown.Mdm2 (murine double minute-2) gene was first cloned as an amplified gene in a spontaneously transformed mouse 3T3 DM cell line [9]. Mdm2 has been shown to interact with a group of cell cycle-related proteins, including the retinoblastoma protein [19], the transcription factor E2F1 [32], and transforming growth factor-beta [28]. Mdm2 is frequently overexpressed in soft tissue sarcomas in human beings [6] and dogs [25,27], and also in some human epithelial neoplasms, such as those of the breast [10,18] The function of p53 tumor suppressor is a principal mediator of growth arrest, senescence, and apoptosis in response to a broad array of cellular damage [17,31]. Mdm2 protein binds to p53 protein, and both proteins regulate each other; one effect is to inhibit the transcriptional transactivation activity of p53, resulting in negative regulation of the tumor suppression function of p53 [21,30]. p53 protein regulates Mdm2 gene at the level of transcription by an intronic promotor. This creates a feedback loop that regulates both the activity of p53 protein and the expression of Mdm2 gene [21,30]. Overexpression of p53 protein has been reported in feline mammary gland tumors and squamous cell carcinomas [22], and in human malignant epithelial tumors of the breast [3], stomach [13], kidney [11], and liver [7].The expression of Mdm2 in feline mammary gland tumors has not been studied. The purpose of this study was to better understand the mechanisms of feline mammary gland tumorigenesis by immunohistochemical means for the nuclear reactivity of Mdm2 and p53 proteins and the relationship between expression of these molecules. MATERIALS AND METHODS Tumors:The samples were collected from feline mammary tumors removed surgically during a 5-year period at Yamaguchi University. The samp...

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MDM2/p53 protein expression in the development of colorectal adenocarcinoma,

Cited by 37 publications

References 25 publications

Potential Role of Apoptosis and Apoptotic Regulatory Proteins in Colorectal Neoplasia: Correlations with Clinico-Pathological Parameters and Survival

Potential Role of Apoptosis and Apoptotic Regulatory Proteins in Colorectal Neoplasia: Correlations with Clinico-Pathological Parameters and Survival

mdm2-p53 Interaction: Lack of Correlation with the Response to 5-Fluorouracil in Advanced Colorectal Cancer

Immunohistochemical Detection of Mdm2 and p53 in Feline Mammary Gland Tumors

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