The role of p53 as a surrogate marker for chemotherapeutical responsiveness in ovarian cancer

Bauerschlag, Dirk; Schem, Christian; Weigel, Marion T.; Kaisenberg, Constantin von; Strauß, Alexander; Bauknecht, Thomas; Maass, Nicolaì; Meinhold‐Heerlein, Ivo

doi:10.1007/s00432-009-0639-8

Cited by 8 publications

(8 citation statements)

References 49 publications

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“…TP53 mutations detected by sequencing methods were found to be 57.5% in the study of Bauerschlag et al [13] and 73% in high-grade serous carcinoma in the study of Wong et al [19]. The mutation prevalences of the other studies are shown in Table 3.…”

Section: Resultsmentioning

confidence: 73%

“…The quality of the included papers ranged between good [14, 16, 17] and moderate [12, 13, 15, 18, 19]. Overall the articles were according to our research question and of fairly good quality.…”

Section: Resultsmentioning

confidence: 99%

“…KRAS was the most frequently investigated gene, followed by PIK3CA . The material used for sequencing, formalin-fixed, paraffin-embedded [12, 17, 18], fresh frozen [15, 19], or both [13, 14, 16] differed among the studies (Table 2). …”

Section: Resultsmentioning

confidence: 99%

“…Despierre et al found that PIK3CA is most common in tumours with FIGO stage Ia–IIc, and that the prevalence is the highest in clear-cell carcinomas (46.2%). Bauerschlag et al [13] did not report any data on KRAS mutations but looked into TP53 mutations in ovarian cancer instead. They showed that the TP53 mutation rate increases when cell differentiation decreases.…”

Section: Resultsmentioning

confidence: 99%

“…In type I tumours (low-grade serous, mucinous, endometrioid, clear-cell) KRAS and BRAF are often mutated [12, 14, 22] whereas TP53 mutations are rare; type II tumours (high-grade serous, undifferentiated cancers, carcinosarcomas) on the other hand harbour often TP53 mutations [22, 23]. TP53 mutation frequencies have been described in high-grade tumours occurring in 58 [13], 73 [19], and 96% [24]. We identified a TP53 mutation frequency in ovarian tumours of 100%, but note that the sample size was only 3.…”

Section: Discussionmentioning

confidence: 99%

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Next-Generation Sequencing in Gynaecological Tumours: The Prognostic and Predictive Value of the Most Common Mutations Found in Ovarian, Endometrial, and Cervical Tumours: Literature Review and the University Medical Centre Utrecht Next-Generation Sequencing Data

et al. 2017

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Objective: To investigate whether next-generation sequencing (NGS) in ovarian and endometrial tumours can discover mutations with a relevant prognostic or predictive value. Methods: After a literature search, selected studies were critically appraised using the Quality in Prognostic Studies tool. Data on mutation incidence and correlations with prognostic and predictive items were extracted from relevant studies and compared to our own cohort consisting of 28 patients analysed using NGS. Results: Eight out of 739 articles were found eligible, including different tumour types. Prevalence of mutations in the KRAS gene ranged between 5.34 and 58.8% in ovarian cancer. Two studies showed a significant correlation between KRAS mutations and an improved disease free- and overall survival. Clinical data were available for 17 of our patients, mostly cases of endometrial carcinomas. KRAS, PIK3CA, CTNNB1, and TP53 were the most frequently mutated genes in endometrial carcinomas, and PTEN and CTNNB1 correlated with a higher FIGO stage. Conclusion: In the ovary KRAS mutation is associated with type I ovarian tumours (low-grade serous, mucinous, endometrioid, and clear-cell) and may seem to have a more favourable prognosis. The prognostic value of TP53 is still controversial. In endometrial tumours, PTEN shows a positive correlation with better prognosis. PIK3CA may have a correlation with poorer prognosis. CTNNB1 mutations in endometrial carcinomas could predict a worse prognosis.

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Section: Resultsmentioning

confidence: 73%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Next-Generation Sequencing in Gynaecological Tumours: The Prognostic and Predictive Value of the Most Common Mutations Found in Ovarian, Endometrial, and Cervical Tumours: Literature Review and the University Medical Centre Utrecht Next-Generation Sequencing Data

et al. 2017

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Mutant p53 and the Response to Chemotherapy and Radiation

Tchelebi

Ashamalla

Graves

2014

Subcellular Biochemistry

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In addition to playing roles in the genesis and progression of cancer, mutant p53 also appears to play a significant role in the response to cancer therapy. In response to chemotherapy and radiation, two mainstays of cancer treatment, most cancer cells harboring p53 mutations show a reduced sensitivity compared to cells lacking p53 or those with wild type p53. However, there are also many instances where mutant p53 has shown no effect or enhances cellular sensitivity to chemotherapy and radiation. Similar to the in vitro cellular studies, the majority of clinical studies show a correlation between the presence of mutant p53 in patient tumors and adverse outcomes following treatment with chemotherapy agents or radiation in comparison to tumors with wild-type p53. However, it still remains unclear whether the presence of mutant p53 in tumors can serve as a reliable prognostic factor and aid in treatment planning. Thus, as genomic analysis of patient tumors becomes more cost effective, the role of mutant p53 in tumor responses from cancer therapy ultimately needs to be addressed. This chapter will discuss current mechanisms of how p53 mutations affect cellular responses to chemotherapy and radiation and discuss patient outcomes based on p53 status.

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Die Heterogenität des Ovarialkarzinoms

et al. 2011

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The role of p53 as a surrogate marker for chemotherapeutical responsiveness in ovarian cancer

Abstract: In this study, the p53 mutational status was not predictive for responsiveness to platinum-based chemotherapy; but p53 was significantly more frequently mutated in poorly differentiated OCs.

Cited by 8 publications

References 49 publications

Next-Generation Sequencing in Gynaecological Tumours: The Prognostic and Predictive Value of the Most Common Mutations Found in Ovarian, Endometrial, and Cervical Tumours: Literature Review and the University Medical Centre Utrecht Next-Generation Sequencing Data

Next-Generation Sequencing in Gynaecological Tumours: The Prognostic and Predictive Value of the Most Common Mutations Found in Ovarian, Endometrial, and Cervical Tumours: Literature Review and the University Medical Centre Utrecht Next-Generation Sequencing Data

Mutant p53 and the Response to Chemotherapy and Radiation

Die Heterogenität des Ovarialkarzinoms

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