p53 mutation does not affect prognosis in ovarian epithelial malignancies

Fallows, Sas; Price, John; Atkinson, R.; Johnston, Patrick G.; Hickey, Ivor; Russell, S. E. H.

doi:10.1002/path.857

Cited by 55 publications

(49 citation statements)

References 29 publications

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“…Within Europe, the data from the following countries/regions were available: Poland, Germany (Kappes et al 1995;Meinhold-Heerlein et al 2001), Norway (Skomedal et al 1997;Smith-Sorensen et al 1998;Wang et al 2004aWang et al , 2004b, the United Kingdom (Jacobs et at. 1992;Milner et al 1993;Foulkes et al 1995;Sarhanis et al 1996;Tavassoli et al 1996;Fallows et al 2001), and France and Italy (Mazars et al 1991;Righetti et al 1996;Lavarino et al 2000). The last group was combined from two countries because of the low number of mutations published from each of these countries, and existence of reports that evaluated data from these two countries together.…”

Section: Comparative Analysis Of the Tp53 Gene Mutational Spectrummentioning

confidence: 99%

Geographical Variations in TP53 Mutational Spectrum in Ovarian Carcinomas

Dansonka-Mieszkowska

Ludwig

Kraszewska

et al. 2006

Annals of Human Genetics

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SummaryThe TP53 gene mutational spectrum in human tumours shows variations related to tissue of origin, carcinogen exposure or molecular background. We have compared TP53 mutations in ovarian carcinomas from different geographical regions; this study was based on data extracted and verified from the IARC database (R10, 2005), and on our results from 127 carcinomas. In total 873 mutations were evaluated. Tumours from Japan and Korea had a higher frequency of exon 7 mutations (38% vs 25%, p = 0.011) and lower frequency of exon 8 mutations (11% vs 29%, p = 0.0003) than those from Western countries; they were particularly different from Norwegian tumours which showed the lowest proportion of exon 7 (19%, p = 0.001) and highest proportion of exon 8 (37%, p < 0.0001) mutations. There were also differences in the profile of TP53 hotspots. The third hotspot in tumours from Poland was amino acid (AA) 176 (8.2% of substitutions vs 1.7% in other countries, p < 0.001), while in tumours from the UK it was AA 220 (8.9% vs 2.3%, p < 0.001). Codon 273 was the only apparent hotspot in the Norwegian tumours, while it was rarely mutated in Polish and Asian tumours. In contrast to other data tumours from Norway presented with 273 HIS codon (82% of mutations at AA 273, p = 0.002), while tumours from the UK shared the 273 CYS codon (80%, p < 0.001). Further analysis of TP53 gene mutations in ovarian cancer by geography could provide greater insights.

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Section: Comparative Analysis Of the Tp53 Gene Mutational Spectrummentioning

confidence: 99%

Geographical Variations in TP53 Mutational Spectrum in Ovarian Carcinomas

Dansonka-Mieszkowska

Ludwig

Kraszewska

et al. 2006

Annals of Human Genetics

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“…in ovarian carcinomas (Kupryjańczyk et al, 1993;Casey et al, 1996;DiCioccio et al, 1998;Wen et al, 1999), studies on TP53 status and tumour response to cisplatin-based chemotherapy have not so far given equivocal results (Righetti et al, 1996;de Feudis et al, 1997;Baekelandt et al, 1999;Eisenhauer et al, 1999;Fallows et al, 2001;Reles et al, 2001).…”

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confidence: 99%

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen

et al. 2003

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In cell line studies, BCL-2, BAX, as well as novel MEK1 protein levels have strong influence on ovarian cancer response to cisplatinbased chemotherapy. However, such associations have not been demonstrated clinically. We evaluated prognostic/predictive significance of these proteins with regard to TP53 status. Immunohistochemical analysis was performed on 229 ovarian carcinomas FIGO stage IIB -IV treated with platinum-based chemotherapy; the results were analysed by the Cox and logistic regression models. Clinical parameters (residual tumour size, patient age, FIGO stage) were the only indicators of overall survival (OS) and the strongest predictors of complete remission (CR). On the other hand, BAX expression was the strongest (P ¼ 0.005) or the only (in FIGO IIIC, P ¼ 0.02) prognostic indicator of disease-free survival (DFS) in the TP53(+) group. TP53(+) and TP53(À) ovarian carcinomas differed in clinical and molecular prognostic and predictive factors. Another novel finding is that CR was negatively influenced by high BAX expression in all patients group (P ¼ 0.047) and by BCL2 expression in the TP53(À) group (P ¼ 0.05). High MEK1 expression was associated with endometrioid and clear cell carcinomas (P ¼ 0.049); its loss was found with advancing FIGO stage (P ¼ 0.002). Our results suggest that binomial TP53 status divides ovarian carcinomas into two biologically distinct groups. BAX expression is an important factor of DFS in the TP53(+) group. BCL-2 and BAX, but not MEK1 expressions have predictive value in ovarian cancer patients treated with platinum-based chemotherapy.

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“…However, microdeletions, insertions and nonsense mutations have also been described (Sood et al, 1999;Buller et al, 2001). A number of studies have analysed ovarian carcinomas for TP53 mutations, but mostly in advanced stages (Kohler et al, 1993;Kupryjanczyk et al, 1993Kupryjanczyk et al, , 1995Fallows et al, 2001;Reles et al, 2001;Leitao et al, 2002). The frequency of mutations was reported to be in the range of 29 -79% depending on the stage of the disease, with the highest frequency found in tumours from patients diagnosed with late-stage disease.…”

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confidence: 99%

TP53 mutations in early-stage ovarian carcinoma, relation to long-term survival

et al. 2004

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We conducted the present study to evaluate the frequency and prognostic importance on long-term survival of TP53 mutations and TP53 protein accumulation in a cohort of 178 patients with early-stage ovarian carcinomas. TP53 mutations scored as aberrant temporal temperature gradient gel electrophoresis pattern from all exons were observed in 39.9% of the tumours. Full screening of exons 5 -8, followed by sequencing, was successful in 135 cases, and 48 mutations altering the protein were detected in 39 cases (28.9%). TP53 mutations were slightly less common in the Federation of Gynecologists and Obstetricians stage IA than in IB/IC (P ¼ 0.05). No significant correlations with histological type, grade of differentiation, DNA ploidy status or age at diagnosis were found. TP53 protein accumulation analysed by immunohistochemistry was found in 32.6% of all tumours, and was a poor predictor of TP53 mutations with 56.4% sensitivity, 77.1% specificity, 50% positive predictive value and 81.3% negative predictive value. Neither TP53 mutations nor TP53 protein accumulation influenced the prognosis significantly in this group of patients.

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p53 mutation does not affect prognosis in ovarian epithelial malignancies

Cited by 55 publications

References 29 publications

Geographical Variations in TP53 Mutational Spectrum in Ovarian Carcinomas

Geographical Variations in TP53 Mutational Spectrum in Ovarian Carcinomas

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen

TP53 mutations in early-stage ovarian carcinoma, relation to long-term survival

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