Clinical Relevance of Immunohistochemical Expression of p53-targeted Gene Products mdm-2, p21 and bcl-2 in Breast Carcinoma

Bànkfalvi, Àgnes; Tory, Kálmán; Kemper, Mechthild; Breukelmann, Dirk; Cubick, Christiane; Poremba, Christopher; Füzesi, L.; Lellé, Ralph J.; Böcker, W.

doi:10.1016/s0344-0338(00)80051-5

Cited by 25 publications

(16 citation statements)

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“…HER-2/neu(erbB2) is one of the proto-oncogene, a member of epidermal growth factor receptor superfamily.Its over expression and gene amplifi cation leads to transformation of human breast epithelium to malignancy. Alterations in the proto-oncogene HER-2/neu have been extensively studied in Western and east Asian females with breast cancer and proposed as prognostic markers of potential clinical utility [11][12][13][14][15][16][17]. However, few studies exist on prognostic signifi cance of these oncogenes in female breast cancer in developing countries particularly in India [18].…”

Section: Introductionmentioning

confidence: 99%

Significance of Her-2/neu protein over expression in Indian breast cancer patients

et al. 2007

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Background Racial disparity in presentation and outcome of breast cancer is established but cause is unexplained . Many studies show various molecular markers for racial differences in the prognosis of breast cancer. There is scarcity of data on prognostic signifi cance of HER-2/neu in Indian breast cancer. Aims and ObjectiveTo know incidence and prognostic signifi cance of HER-2/neu expression in Indian patients.To correlate HER-2/neu Expression with other prognostic markers and ER/PR Receptor status. Statistical Analysis Data was analyzed by univariate and multivariate analysis for all prognostic factors. Signifi cance was calculated by using Chi square test and survival analysis by using Kaplan Meier survival curve. Material and MethodsResults The median age of 112 patients was 46.56 (±9.55) years. HER-2/neu over expression was present in 46.37%. Signifi cant correlation was found between HER-2/neu over expression and lymph node status, grade of tumor and ER/ PR receptor status. Median follow up period of 23 months. There was signifi cant tumour free survival advantage (p < 0.01) and overall survival advantage (p < 0.001) in patients with HER-2/neu negative expression.Conclusion HER-2/neu oncogene over expression is higher (46.37%) among Indian patients in comparison to 25-30% shown in most western literature. HER-2/neu oncogene over expression signifi cantly correlates with grade, lymph node involvement, ER/PR status and also affects survival.

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Section: Introductionmentioning

confidence: 99%

Significance of Her-2/neu protein over expression in Indian breast cancer patients

et al. 2007

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“…waf-1 or TSP-1 protein levels were found to associate with the size or grade of invasive breast carcinomas, despite correlating with prognosis (5,8,9,11,12).…”

Section: Discussionmentioning

confidence: 98%

“…The findings reported above suggested earlier that measuring the expression of p53 or its transcriptional targets could monitor human DBC progression, having a prognostic relevance. However, studies evaluating this possibility gave contrasting results (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). This could depend on the fact that DBC expression of p53 or its targeted molecules was assayed mostly at the protein level.…”

Section: Introductionmentioning

confidence: 99%

Correlation between pathological data and the RNA expression of p53 or p53-targeted genes in primary invasive ductal breast carcinomas: A preliminary study

Albonici

Sorge²,

Santeusanio³

et al. 2010

Oncol Rep

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Abstract. The protein expression of the growth suppressive p53 transcription factor and its inhibitor human double minute 2 (Hdm2) is altered in ductal breast carcinomas (DBC). However, the assessment of p53 and/or Hdm2 protein levels in DBC tissues was found to have a questionable prognostic significance. We evaluated the RNA expression of p53, hdm2, and the p53-targeted p21waf-1 and thrombospondin (tsp)-1 by primary DBC tissues, then correlated the RNA levels with patient clinicopathological data. The mean RNA expression level of p53 and that of hdm2 were elevated in large-sized, poorly differentiated, node-positive DBC, while a high p21waf-1 or tsp-1 mean expression level comprised small-sized, low-grade, node-negative tumors. Further analyses found that the correlation between the RNA expression of p53 and that of its targeted genes was reduced as tumor aggressiveness increased. However, for all the examined genes, association of the intensity of RNA expression with the pathological data was not statistically significant (p>0.05). Altogether, our preliminary RNA data confirm the results from previous protein studies, indicating that despite p53 expression and activity show a trend to vary in association with DBC clinical features, neither p53 nor its transcriptional targets can accurately monitor the behaviour of invasive DBC.

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“…Expression of Mdm2 is consequent upon p53 activation. Concomitant overexpression of Mdm2 and p53 has been observed in human epithelial neoplasms including those of the breast [3,4], prostate [16], stomach [13], liver [7], and bladder [29] and associated with high tumor grade and tumor invasiveness and aggressiveness. A reciprocal relationship between the presence of a p53 mutation and Mdm2 gene amplification was demonstrated in canine soft-tissue sarcomas [25].…”

Section: Discussionmentioning

confidence: 99%

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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Clinical Relevance of Immunohistochemical Expression of p53-targeted Gene Products mdm-2, p21 and bcl-2 in Breast Carcinoma

Cited by 25 publications

References 49 publications

Significance of Her-2/neu protein over expression in Indian breast cancer patients

Significance of Her-2/neu protein over expression in Indian breast cancer patients

Correlation between pathological data and the RNA expression of p53 or p53-targeted genes in primary invasive ductal breast carcinomas: A preliminary study

Immunohistochemical Detection of Mdm2 and p53 in Feline Mammary Gland Tumors

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