| 1. |
- Stenmark-Askmalm, Askmalm Marie, 1966-, et al.
(författare)
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Protein accumulation and gene mutation of p53 in bilateral breast cancer
- 2001
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 40:1, s. 56-62
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the frequency of p53 alterations in bilateral breast cancer and to evaluate a possible clonal relationship between the paired tumours regarding p53 alteration and other pathobiological variables. Tumours from 34 patients were investigated with immunohistochemistry, single strand conformation polymorphism analysis and DNA-sequence analysis applied to exons 5-8. Fifteen percent of the 68 tumours showed positive immunoreaction and/or presence of mutation. The occurrence of p53 accumulation was 9% and the prevalence of gene mutation 10%. No significant concordance was found between the tumours in the same patient for p53 alterations, progesterone receptor status or DNA ploidy. S-phase fraction showed a weak correlation, not statistically significant. Oestrogen receptor status was the only variable that exhibited a significant concordance. No convincing evidence was found for other associations between the paired tumours or for a high prevalence of p53 alterations in bilateral breast cancer.
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| 2. |
- Stenmark Askmalm, Marie, et al.
(författare)
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Mutation and accumulation of p53 related to results of adjuvant therapy of postmenopausal breast cancer patients
- 2004
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 43:3, s. 235-244
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Tidskriftsartikel (refereegranskat)abstract
- p53 protein accumulation and gene mutation have been implicated in resistance to cytotoxic treatment. This study was performed to further assess the predictive value of p53 in breast cancer. Postmenopausal patients were randomized to adjuvant chemotherapy with cyclophosphamide, metothrexate, or 5-fluorouracil (CMF) vs. Postoperative radiotherapy. The patients were also randomized to adjuvant tamoxifen vs. No endocrine treatment. Immunohistochemistry (IHC) and single-strand conformation polymorphism (SSCP), followed by direct sequencing, was performed. The p53 altered group, regarded as positive for p53 gene mutation and/or p53 protein accumulation, tended to benefit more from CMF than from radiotherapy as compared with others regarding distant recurrences. In the group lacking p53 alteration there was a significantly decreased local recurrence rate in the radiotherapy group as compared with the CMF group (RR = 0.24, 95% CI = 0.083-0.62), whereas no benefit from radiotherapy was found for patients snowing p53 alterations. Tamoxifen significantly decreased the rate of distant recurrence for estrogen receptor-positive patients with no apparent difference in relation to p53 alteration. It is suggested that p53 alteration indicates benefit from CMF compared with radiotherapy regarding distant recurrence-free survival and the best local control with radiotherapy is achieved in the absence of p53 alteration. Finally, altered p53 status is probably not a marker of resistance to tamoxifen.
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