Poor survival with wild-type TP53 ovarian cancer?

Wong, Kwong-Kwok; Izaguirre, Daisy I.; Kwan, Suet Yan; King, Erin R.; Deavers, Michael T.; Sood, Anil K.; Mok, Samuel C.; Gershenson, David M.

doi:10.1016/j.ygyno.2013.06.016

Cited by 42 publications

(47 citation statements)

References 31 publications

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“…Of note, a recent study analyzing the clinical data from the TP53 mutation-negative cases in the ovarian TCGA reported that women with TP53 mutation-negative tumors had a significantly shorter survival and their tumors had higher chemoresistance compared with the TP53 -mutated cases (39). These findings should be interpreted in the light of our study showing that nearly all of the “ TP53 mutation-negative”cases were misclassified highlighting the importance of rigorous pathology rereview.…”

Section: Discussionmentioning

confidence: 99%

Molecular Alterations of TP53 are a Defining Feature of Ovarian High-Grade Serous Carcinoma

Vang

Levine

Soslow

et al. 2016

International Journal of Gynecological Pathology

135

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Summary The Cancer Genome Atlas has reported that 96% of ovarian high-grade serous carcinomas (HGSCs) have TP53 somatic mutations suggesting that mutation of this gene is a defining feature of this neoplasm. In the current study, 5 gynecologic pathologists independently evaluated hematoxylin and eosin slides of 14 available cases from The Cancer Genome Atlas classified as HGSC that lacked a TP53 mutation. The histologic diagnoses rendered by these pathologists and the accompanying molecular genetic data are the subject of this report. Only 1 case (Case 5), which contained a homozygous deletion of TP53, had unanimous interobserver agreement for a diagnosis of pure HGSC. In 1 case (Case 3), all 5 observers (100%) rendered a diagnosis of HGSC; however, 3 observers (60%) noted that the histologic features were not classic for HGSC and suggested this case may have arisen from a low-grade serous carcinoma (arisen from an alternate pathway compared with the usual HGSC). In 2 cases (Cases 4 and 12), only 3 observers (60%) in each case, respectively, interpreted it as having a component of HGSC. In the remaining 10 (71%) of tumors (Cases 1, 2, 6–11, 13, and 14), the consensus diagnosis was not HGSC, with individual diagnoses including low-grade serous carcinoma, high-grade endometrioid carcinoma, HGSC, metastatic carcinoma, clear cell carcinoma, atypical proliferative (borderline) serous tumor, and adenocarcinoma, not otherwise specified. Therefore, 13 (93%) of the tumors (Cases 1–4 and 6–14) were either not a pure HGSC or represented a diagnosis other than HGSC, all with molecular results not characteristic of HGSC. Accordingly, our review of the TP53 wild-type HGSCs reported in The Cancer Genome Atlas suggests that 100% of de novo HGSCs contain TP53 somatic mutations or deletions, with the exception of the rare HGSCs that develop from a low-grade serous tumor precursor. We, therefore, propose that lack of molecular alterations of TP53 are essentially inconsistent with the diagnosis of ovarian HGSC and that tumors diagnosed as such should be rigorously reassessed to achieve correct classification.

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Section: Discussionmentioning

confidence: 99%

Molecular Alterations of TP53 are a Defining Feature of Ovarian High-Grade Serous Carcinoma

Vang

Levine

Soslow

et al. 2016

International Journal of Gynecological Pathology

135

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“…45,46 This concept describes 5 technical standards for open data: online availability (first star), availability as structured data such as an Excel spreadsheet for reuse (second star), availability in nonproprietary formats such as comma-separated values instead of Excel (third star), using uniform resource identifiers such as a web address so users can locate the data online (fourth star), and hyperlinking the data to other relevant data to provide context (fifth star).…”

Section: • Methodsmentioning

confidence: 99%

Evaluating the Quality and Usability of Open Data for Public Health Research: A Systematic Review of Data Offerings on 3 Open Data Platforms

Martin

Law

Ran

et al. 2017

Journal of Public Health Management and Practice

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“…HGOSC almost universally showed p53 gene mutation, followed by genomic instability, DNA copy number abnormalities etc. [16,35]. The PI3K/AKT/mTOR pathway is one of the most important genetic alteration in ovarian cancer, mostly activated due to the mutations in PI3KCA gene.…”

Section: Important Clinicopathologic and Genetic Alterationsmentioning

confidence: 99%

“…Recent genomic analysis of The Cancer Genome Atlas reported mutations in p53 gene in 96% of 316 cases of high-grade ovarian serous carcinoma (HGOSC) [16]. Other important genetic changes affect phosphatidyinositol-3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) cascade.…”

Section: Introductionmentioning

confidence: 99%

Anticancer Strategy Targeting Mitochondrial Biogenesis in Ovarian Cancer

Uddin¹,

Kim²,

Suh³

et al. 2014

J Cancer Sci Ther

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IntroductionOvarian cancer is the most lethal gynecologic malignancy worldwide typically in the post-menopausal women and 5 th leading cause of death in the United States [1][2][3]. About 80% of women are diagnosed at the advanced-stage of disease and have poor prognosis. The 5-year overall survival rate is 45% or below [4][5][6]. Despite the first complete response after the front-line platinum-based chemotherapeutic drugs [7,8], approximately 25% patients suffer from relapse within 6 months who are thought, by definition, to have a chemoresistance [9][10][11][12]. Combination of platinum and other drugs might improve the survival rate [13], but is not out of the danger of additive toxicity [14].Several genetic alterations have been observed in ovarian cancer, involving deactivation mutations in tumor suppressor genes, such as p53, BRCA1 and BRCA2, and activation mutation and/or amplification of proto-oncogenes, like c-MYC, KRAS and AKT [15]. Recent genomic analysis of The Cancer Genome Atlas reported mutations in p53 gene in 96% of 316 cases of high-grade ovarian serous carcinoma (HGOSC) [16]. Other important genetic changes affect phosphatidyinositol-3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) cascade. The mTOR plays a central role in energy metabolism, cell growth/division through macromolecular synthesis and is found to be activated in ovarian cancer [6], which indicates a close relationship between genetic alteration and energy metabolism. It was observed that hexokinase (HK) II, the rate limiting initial enzyme in glycolysis, is overexpressed in ovarian cancer [12]. The genetic alterations and subsequent metabolic remodeling have been found to be associated with the chemoresistance [17], such as association of rictor (mTORC2 component) with resistance to cisplatin [2]. Cisplatin-induced caspase activation causing PTEN cleavage has also been reported as a potential mechanism of chemoresistance in ovarian cancer [18].Mitochondria is a well-adapted endosymbiotic intracellular organelles, became efficient for energy production through-out the course of evolution [19]. They are critical for survival and proliferation of living organisms under aerobic conditions and produce ATP through oxidative phosphorylation (OXPHOS) [20]. Beyond the conventional function they have crucial role in certain neurodegenerative diseases and cancer [21][22][23]. Cellular proliferation largely depends on mitochondrial amount, governed by the process of MtBIO [20]. MtBIO is the production of daughter mitochondria usually from previously existed one through a division process of called fission, subsequent growth, and maintenance by fusion and autophagy of mitochondria (mitophagy) [24]. Currently it has been observed that MtBIO is associated with cancer chemoresistance [25,26] through the modulation of associated proteins such as methylation-controlled J-protein (MCJ, also known as DNAJC15) [25,27], prohibitin 1 (PHB-1) [28][29][30], myeloid cell leukemia sequence 1 (MCL-1) [31,32] etc. in ovarian cancer. Thus it can be s...

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Poor survival with wild-type TP53 ovarian cancer?

Cited by 42 publications

References 31 publications

Molecular Alterations of TP53 are a Defining Feature of Ovarian High-Grade Serous Carcinoma

Molecular Alterations of TP53 are a Defining Feature of Ovarian High-Grade Serous Carcinoma

Evaluating the Quality and Usability of Open Data for Public Health Research: A Systematic Review of Data Offerings on 3 Open Data Platforms

Anticancer Strategy Targeting Mitochondrial Biogenesis in Ovarian Cancer

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