p53 protein and vimentin m invasive ductal NOS breast carcinoma—relationship with survival and sites of metastases

Domagała, W; Striker, G.; Szadowska, A; Dukowicz, Andrzej; Harezga, Barbara; Osborn, Mary

doi:10.1016/0959-8049(94)00288-g

Cited by 39 publications

(24 citation statements)

References 29 publications

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“…However, due to the lack of functional studies on these tumours, the biological signi®cance of such observations remains unclear. The incidence of TP53 alteration has been reported to be dependent on the histological type (Domagala et al, 1993). In¯ammatory breast carcinomas represent 1 ± 2% of primary breast cancers (Jaiyesimi et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

p21WAF1/CIP1 response to genotoxic agents in wild-type TP53 expressing breast primary tumours

et al. 1997

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Functional inactivation of the wild-type p53 protein has been described in di erent human cancers. Since a signi®cant proportion of breast tumours express wildtype TP53, the p53 antiproliferative activity could be inactivated in transformed mammary epithelial cells by a mechanism independent on structural alteration of the gene. To test this hypothesis, we analysed the p53 activity in primary breast tumour cells. As a preliminary study, we demonstrated in breast adenocarcinoma cell lines that the nuclear accumulation of the inhibitor of cyclin dependent kinase p21 WAF1/CIP1 , in response to adriamycin treatment, speci®cally re¯ected the activity of a functional wild-type p53 protein. Then, we used this strategy to study the p53 activity in 23 primary breast tumours. p21 WAF1/CIP1 accumulation was detected in all tumours expressing wild-type TP53. In contrast, no p21 WAF1/CIP1 response was detected in cells harboring a mutant TP53 gene. This report is the ®rst functional study of p53 in primary breast tumours. The results demonstrate that TP53 mutation represents the only common mechanism leading to an irreversible inactivation of p53 functions in this cancer type.

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Section: Discussionmentioning

confidence: 99%

p21WAF1/CIP1 response to genotoxic agents in wild-type TP53 expressing breast primary tumours

et al. 1997

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“…The patient follow-up ranged from a minimum of 28 months to more than 10 years; only five studies however, had a follow-up of at least 10 years. Disease-free (DFS) and overall survival (OS) were reported by most, but not all authors; multivariate, analysis was available in about half of these investigations [2,3,5,33,36,51,53,67,90,99,136,145,146]. Most importantly, data on p53 genotype were available, at least in part, in only 5 of the 22 papers reviewed: the remaining investigations relied exclusively on immunohistochemical data.…”

Section: Breast Cancermentioning

confidence: 94%

The clinical significance of p53 aberrations in human tumours

Bòsari

Viale

1995

Vichows Archiv A Pathol Anat

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p53 aberrations are the most common genetic alteration found in human tumours and this review summarizes the current understanding of the clinical significance of p53 abnormalities. Immunohistochemical and molecular techniques can demonstrate alterations at the protein and gene level, respectively, but with a significant discordance between the findings of either technique. The tumours evaluated in this review include cancers of the breast, lung, gastrointestinal tract, genitourinary tract, and others. In most cases, only data on p53 protein are available and in each of these tumour types discrepant conclusions on the clinical value of p53 abnormalities as prognostic indicators have been reached. The role of p53 in the context of anticancer adjuvant therapy has also been analysed. Experimental data suggest that p53 affects the apoptotic response to anticancer agents, but this has not yet been proven in a clinical series where this demonstration and its effect on therapy could represent one of the most important endpoints in p53 clinical research. The use of standardized techniques to evaluate p53 gene mutation and protein accumulation within controlled clinical series of patients entering prospective trials is essential to answer the many remaining questions on the clinical significance of p53 aberrations.

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“…In the node-negative group of patients, 36 (28%) received adjuvant chemotherapy (CMF), 12 (9%) received adjuvant hormonotherapy (tamoxifen), and eight (6%) received adjuvant chemo-and hormonotherapy. In addition, p53 status was available for 221 tumors tested with the monoclonal p53 antibody, DO1, from results published previously [12], while the MIB-1 score was known for 192 tumors from results also published previously [13].…”

Section: Patients and Tumor Materialsmentioning

confidence: 99%

“…The issue of p53 and prognosis in breast carcinoma is still controversial [3]. p53 mutations are found in 17-33% of breast carcinomas by DNA sequencing [2,9,26,33,37], and an accumulation of p53 is noted in 23-52% using histochemistry [1,12,20,35,38]. Such tumors also have a high growth fraction, presumably because tumor cells with p53 mutations that result in p53 accumulation are released from p53-mediated growth arrest.…”

Section: Introductionmentioning

confidence: 99%

p21/WAF1/Cip1 expression in invasive ductal breast carcinoma: relationship to p53, proliferation rate, and survival at 5 years

et al. 2001

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The p21/WAF1/Cipl antibody, DCS-60, was characterized by means of immunoblotting and immunofluorescence on a variety of human breast cancer cell lines. Heterogeneous staining of nuclei was observed with strong staining of cells in early G1. p21/WAF1/Cipl expression in invasive ductal, not otherwise specified breast carcinomas was determined using immunohistochemistry with this antibody and computerized image analysis. Two hundred and twenty-two tumors, including 130 from patients with no axillary node involvement, were examined. p21-positive tumor cell nuclei were found in 30% of the breast carcinomas. The percentage of tumor cell nuclei that were positive ranged from less than 1% to greater than 10%. In the whole cohort of patients, p21 expression was significantly associated with a low histological grade. In the node-negative group, there was a significant negative correlation between p21 positivity and a high (>10%) MIB-1 score. The mean MIB-1 score was significantly lower in p21-positive tumors in the whole cohort of patients (P=0.03) and in the nodenegative group (P=0.02). No association was found between p21 expression and overall survival at 5 years. With respect to p21/p53 phenotype, the significant difference in survival was noted only for the group of patients treated with adjuvant chemotherapy. The p21- p53+ phenotype had the worst survival (58% surviving 5 years), while the p21+ p53- phenotype had good survival (83% surviving 5 years; P<0.05). The results seem to suggest a correlation between p21/p53 phenotype and response to adjuvant chemotherapy.

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p53 protein and vimentin m invasive ductal NOS breast carcinoma—relationship with survival and sites of metastases

Cited by 39 publications

References 29 publications

p21WAF1/CIP1 response to genotoxic agents in wild-type TP53 expressing breast primary tumours

p21WAF1/CIP1 response to genotoxic agents in wild-type TP53 expressing breast primary tumours

The clinical significance of p53 aberrations in human tumours

p21/WAF1/Cip1 expression in invasive ductal breast carcinoma: relationship to p53, proliferation rate, and survival at 5 years

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