Spontaneous apoptosis in ovarian carcinomas: a positive association with p53 gene mutation is dependent on growth fraction

Kupryjańczyk, Jolanta; Dansonka-Mieszkowska, Agnieszka; Szymanska, T.; Karpińska, G; Rembiszewska, Alina; Rusin, Marek; Konopiński, Ryszard; Kraszewska, Ewa; Timorek, Agnieszka; Yandell, David W.; Stelmachów, J

doi:10.1054/bjoc.1999.0967

Cited by 11 publications

(7 citation statements)

References 28 publications

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“…(Kupryjanczyk et al 2000); # -TP53 accumulation (+), lack of TP53 accumulation (-) has been determined previously (Kupryjanczyk et al 2000(Kupryjanczyk et al , 2003; S-serous, M-mucinous, E-endometrioid, C-clear cell, O-other (transitional cell carcinoma, carcinosarcoma, undifferentiated, unclassified).…”

Section: Tp53 Gene Mutations In the Polish Populationmentioning

confidence: 88%

“…The total number of alterations that resulted in the formation of a truncated protein (also verified immunohistochemically by the lack of TP53 protein accumulation; Kupryjanczyk et al 2000Kupryjanczyk et al , 2003 was 34 out of 103 (33% of all mutations). Two in frame errors (exon 6, tumour 165; exon 5, tumour 172), two splice-site mutations (exon 5, tumour 280; exon 10, tumour 311) and one nonsense mutation (exon 7, tumour 351) resulted in TP53 protein accumulation (Table 1).…”

Section: Tp53 Gene Mutations In the Polish Populationmentioning

confidence: 92%

“…The TP53 gene has been subjected to analysis for ovarian cancer for 14 years now, and its mutations are the most frequent genetic alterations identified in these tumours (range 40-80%, mean 60% from analyses of TP53 Mutational Spectrum in Ovarian Cancer the entire coding sequence) (Kihana et al 1992;Kupryjanczyk et al 1993Kupryjanczyk et al , 1995Kupryjanczyk et al , 2000Casey et al 1996;Skilling et al 1996;DiCioccio et al 1998;Rhei et al 1998;Shigemasa et al 1999;Wen et al 1999). In ovarian carcinomas transitions predominate over transversions and a high percentage of these occur at CpG islands.…”

Section: Introductionmentioning

confidence: 99%

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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: Tp53 Gene Mutations In the Polish Populationmentioning

confidence: 88%

Section: Tp53 Gene Mutations In the Polish Populationmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Geographical Variations in TP53 Mutational Spectrum in Ovarian Carcinomas

Dansonka-Mieszkowska

Ludwig

Kraszewska

et al. 2006

Annals of Human Genetics

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“…K 5204, Dako, Glostrup, Denmark) served as controls for the procedure, as well as for the specificity of the CBE356 antibody. As a positive control for TP53, we used a tumour with a defined TP53 gene missense mutation (Kupryjanczyk et al, 2000). Normal mouse IgGs of the same subclasses and concentrations as the primary antibodies served as negative controls, too.…”

Section: Immunohistochemical Analysismentioning

confidence: 99%

TP53 status determines clinical significance of ERBB2 expression in ovarian cancer

et al. 2004

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ERBB2 expression has been found in 19 to 44% of ovarian carcinomas; however, its predictive value has not been demonstrated, and trastuzumab has not found clinical application in ovarian cancer patients. We evaluated clinical significance of ERBB2 expression in relation to TP53 accumulation in ovarian carcinoma patients treated with platinum-based regimens. Immunohistochemical analysis with CB11 and a novel NCL-CBE356 antibody (against the internal and external domains of ERBB2, respectively) was performed on 233 tumours (FIGO stage IIB-IV); the US Food and Drug Administration-approved grading system with 0 to 3 þ scale was used for evaluation, and the results were analysed by the Cox and logistic regression models. In all, 42% of the tumours expressed (category 1 þ , 2 þ or 3 þ ) either CB11 or CBE356 or both (CB11/CBE356 parameter). Associations between ERBB2 expression and clinical factors were observed only if tumours with staining category 1 þ were grouped together with tumours showing staining categories 2 þ and 3 þ . CB11/CBE356 parameter had a better predictive value than CB11 alone. CB11/CBE356 expression was negatively associated with platinum sensitivity (PS) in the TP53(À) group (P ¼ 0.022) and with disease-free survival (DFS) in the TP53( þ ) group (P ¼ 0.009). Our results may suggest that trastuzumab should be given postoperatively to patients with TP53(À)/ERBB2( þ ) ovarian carcinomas to enhance PS, and after completion of chemotherapy to patients with complete remission and TP53( þ )/ ERBB2( þ ) carcinomas to extend DFS time (in total to 30.4% of all patients analysed). Thus, novel criteria for ovarian cancer patient inclusion for clinical trials with trastuzumab should be considered and tested.

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“…The prognostic value of p53 protein accumulation has been a matter of controversy. It seems that p53 protein accumulation is a more adequate manifestation of impaired p53 protein function than a marker of gene alterations that also may include nonsense errors without protein accumulation (4) . Schildkraut et al (12) have demonstrated in a study on 197 patients with ovarian cancer (72 patients with early and 125 patients with advanced FIGO stages), that p53 overexpression, FIGO stage, and age were independent predictors of survival if the patients at time of diagnosis were younger than 55 years.…”

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confidence: 99%

The prognostic importance of p53, bcl-2, and bax in early stage epithelial ovarian carcinoma treated with adjuvant chemotherapy

Skírnisdóttir¹,

Seidal²,

Gerdin³

et al. 2002

Int J Gynecol Cancer

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Epithelial ovarian cancer is one of the major causes of death among women. The increasing knowledge about molecular events involved in the early stages of ovarian tumorigenesis may provide the basis for management in the future. In a series of 109 patients with epithelial carcinomas in FIGO stages IA-IIC, a number of clinicopathologic prognostic factors (age, FIGO stage, histopathologic type, and tumor grade) were studied in relation to the biologic factors p53, bcl-2, and bax, which are important regulators of apoptosis. Immunohistochemical techniques were used. All the patients received adjuvant chemotherapy after the primary surgery. Univariate analysis showed that expression of p53 was significantly associated with tumor grade (P = 0.014), probability of persistent disease (P = 0.016), and cancer-specific survival rate (P = 0.007). Positive bcl-2 staining was associated with endometrioid tumor subtype (P = 0.029) and a favorable tumor grade distribution (P = 0.034), but not with the survival status. The combined p53-bcl-2 expression was related to histopathologic subtype (P = 0.032), tumor grade (P = 0.011), persistent disease (P = 0.014), and risk of dying due to the disease (P = 0.039). The bax status was not a prognostic factor, but the combined p53-bax expression showed an association with FIGO stage (P = 0.014), tumor grade (P = 0.034), persistent disease (P = 0.006), and risk of dying due to the disease (P = 0.039). The combined bcl-2-bax expression was related to histopathologic subtype (P = 0.045) and tumor grade (P = 0.022). In a multivariate Cox analysis, tumor grade (P = 0.014), and p53 status (P = 0.020) were independent and significant prognostic factors with regard to the cancer-specific survival rate.

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Spontaneous apoptosis in ovarian carcinomas: a positive association with p53 gene mutation is dependent on growth fraction

Cited by 11 publications

References 28 publications

Geographical Variations in TP53 Mutational Spectrum in Ovarian Carcinomas

Geographical Variations in TP53 Mutational Spectrum in Ovarian Carcinomas

TP53 status determines clinical significance of ERBB2 expression in ovarian cancer

The prognostic importance of p53, bcl-2, and bax in early stage epithelial ovarian carcinoma treated with adjuvant chemotherapy

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