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  • 1
    ISSN: 1432-2307
    Keywords: Key words Breast carcinomas ; p53 ; TP53 gene ; E-cadherin ; Immunohistochemistry ; Genomic instability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In breast carcinomas the TP53 gene is altered in 10–30% of cases. Alteration of the gene may lead to a general genomic instability, detected as deletions and/or amplifications at the gene level, and as altered expression at the mRNA and protein level. We have demonstrated a strong association between down-regulation of E-cadherin protein expression and alterations of the p53 protein, detected as TP53 gene mutation and/or protein accumulation in tumour samples from 210 patients with breast carcinomas (P 〈0.001). Investigation of allelic imbalance using microsatellite markers located near the E-cadherin locus was also performed. A higher frequency of loss of heterozygosity in the microsatellite marker closest to the E-cadherin locus was observed in samples with down-regulation of E-cadherin protein expression. A higher frequency of down-regulation of the E-cadherin protein expression was found in invasive lobular carcinomas than in invasive ductal carcinomas, although this difference was of borderline significant (P=0.084). Cases in the present series were also immunostained for c-erbB-2 protein overexpression. A significant association between p53 protein accumulation and cerbB-2 protein overexpression was seen (P=0.036). The results of the present study indicate that p53 protein may play a role in regulation of E-cadherin protein expression.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2307
    Keywords: Key words Breast cancer ; Cyclin D1 ; p53 ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cyclin D1 has been reported to be overexpressed in many tumours, including breast carcinomas. Cyclin D1 was first identified as a protooncogene (BCL1/PRAD1), and its overexpression was related to tumour proliferation. The product has also recently been identified as important in mediating cell cycle growth arrest via the p53 pathway in murin fibroblast cell lines. Ninety breast carcinomas previously analysed for p53 status were analysed for amplification of cyclin D1, D2 and D3 genes by Southern blot analysis and for protein expression by immunhistochemistry. In 10 samples gene amplification was detected at the cyclin D1 locus. No gene amplification was detected at the cyclin D2 and D3 loci. Immunoreactivity for cyclin D1 was detected in 38 (42.2%) tumour tissue samples. Fifty samples were immunostained for cyclin D2 and D3. Only 2 samples (4%) showed immunoreactivty for cyclin D2, and 9 samples (18%) for cyclin D3. Cyclin D1 protein overexpression was significantly more often found in tumours with wild type p53 and in tumours with higher grades of differentiation expressing ER. No association was seen between gene amplification of the cyclin D1 gene and p53 status. We conclude there is a relationship between wild type p53 and cyclin D1 protein overexpression in clinical material, indicating that cyclin D1 may be another downstream effector of p53.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 436 (2000), S. 224-228 
    ISSN: 1432-2307
    Keywords: Key words Apoptosis ; bax ; bcl-2 ; Colon carcinoma ; CyclinD1 ; Immunohistochemistry ; p21 ; p53 ; pRb
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Tumour growth is regulated by a balance between proliferation, growth arrest and programmed cell death (apoptosis). Until recently, the majority of the studies dealing with oncogenesis has been focused on the regulation of cell proliferation. There is now growing understanding that control of growth arrest and apoptosis play key roles in the development of human cancer and in cancer treatment. Some of the more heavily studied proteins of importance for the control of growth arrest and apoptosis are p53, p21, bcl-2 and bax. Alterations in the p53 protein may lead to malignant transformation and defect therapy response, most likely as a result of defective p53-dependent apoptosis. In addition, p21 (WAF1/CIP1) is involved in cell-cycle arrest and probably in induction of p53-dependent apoptosis. Proteins belonging to the bcl-2 family are also important for normal apoptosis. Overexpression of bcl-2 protein is thought to reduce the apoptotic capacity, while bax protein seems to be necessary for induction of apoptosis. In this study, we have immunostained tissues from 93 primary colon carcinomas and have examined the expression of p53, p21 (WAF1/CIP1), bcl-2 bax, pRb and cyclin D1 for evaluation of their roles in colon-cancer progression. A highly significant association between p53 accumulation and downregulation of p21 (WAF1/CIP1) was seen. We also found a strong association between reduced/absent p21 and the development of metastases and death due to cancer disease. Cyclin D1, bcl-2 and bax protein failed to have independent prognostic impacts. Bcl-2 and bax protein levels showed an inverse relationship. The results of the present study indicate that reduced p21 protein levels play an important role in progression of colon cancer. We concluded that evaluation of p21 expression in primary colon carcinomas at the time of surgery might be a valuable tool in defining patients with a high risk of developing metastases.
    Type of Medium: Electronic Resource
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