Malignant Mixed Müllerian Tumors of the Uterus: A Clinicopathologic, DNA Flow Cytometric, p53, and mdm-2 Analysis of 44 Cases

Blom, René; Guerrieri, Claudio; Stål, Olle; Malmström, Henric; Sullivan, S.; Simonsen, Ernst

doi:10.1006/gyno.1997.4892

Cited by 32 publications

(35 citation statements)

References 22 publications

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“…Moreover, p53 expression was similar in primary uterine tumors and paired metastatic lesions [49]. Altogether, most studies published worldwide report a p53 pattern concordance between the epithelial and mesenchymal CS components, with both components being either positive or negative [49,51,84,85,86,87,88,89,90,91,92,93,94,95] (fig. 2).…”

Section: P53 Alterations/expression In Uterine Cssmentioning

confidence: 96%

“…An overall as well as disease-free survival of uterine CS females in relation to p53 pathway alterations has been reported in a limited number of studies published worldwide [17,49,88,94,95,121,122,123]. For example, p53 protein overexpression/ TP53 alterations appeared to have no prognostic utility in 24 uterine CS patients [121].…”

Section: Survival Of Cs Patients In Relation To P53 Pathway Alterationsmentioning

confidence: 99%

“…Interestingly, only half of the tumors were found to harbor alterations either in mdm2 or at p53, suggesting that ‘… mdm2 gene amplification might be an alternative mechanism overcoming p53-dependent tumor-growth suppression ...' [109]. Blom et al [88] reported mdm2 overexpression in 25% (11 out of 43) of uterine CSs; simultaneous overexpression of p53 and mdm2 was observed in 7 homologous tumors but only in 1 heterologous tumor. All p53-positive neoplasms revealed a concordant immunostaining pattern of both tumor components, suggesting a monoclonal nature of MMMTs of the uterus [88].…”

Section: Mouse Double Minute 2 Homolog Overexpression/alterations In mentioning

confidence: 99%

“…Blom et al [88] reported mdm2 overexpression in 25% (11 out of 43) of uterine CSs; simultaneous overexpression of p53 and mdm2 was observed in 7 homologous tumors but only in 1 heterologous tumor. All p53-positive neoplasms revealed a concordant immunostaining pattern of both tumor components, suggesting a monoclonal nature of MMMTs of the uterus [88]. In contrast, Kanthan et al [94] described Mdm2 expression only in 17.4% (4 of 23) of uterine CSs.…”

Section: Mouse Double Minute 2 Homolog Overexpression/alterations In mentioning

confidence: 99%

“…Mdm2 overexpression leads to the inactivation of wild-type p53, as do the alterations in TP53 [103,104,105]. A few case studies have only evaluated the alterations of mdm2 in various primary human sarcomas and CSs, including esophageal [106], submandibular gland [107], blastomatoid pulmonary [108], and uterine [88,94,109] tumors. Investigating uterine sarcomas, Japanese researchers reported mdm2 amplification in 4 of 12 (33%) cases [109].…”

Section: Mouse Double Minute 2 Homolog Overexpression/alterations In mentioning

confidence: 99%

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Role of p53 Pathway Alterations in Uterine Carcinosarcomas (Malignant Mixed Müllerian Tumors)

et al. 2014

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Carcinosarcomas (CSs; malignant mixed Müllerian tumors) of the uterus are highly malignant neoplasms characterized by an unfavorable outcome. They represent less than 5% of all uterine malignancies, and the median patient survival rate is only 21 months. p53 pathway alterations have been studied in CSs originating from the uterus, supporting the monoclonal nature of most but not all of these neoplasms. This paper gives an overview of the current knowledge of p53 pathway distortions in patients with uterine CSs. The survival of patients with uterine CSs in relation to p53 pathway alterations is also briefly summarized.

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Section: P53 Alterations/expression In Uterine Cssmentioning

confidence: 96%

Section: Survival Of Cs Patients In Relation To P53 Pathway Alterationsmentioning

confidence: 99%

Section: Mouse Double Minute 2 Homolog Overexpression/alterations In mentioning

confidence: 99%

Section: Mouse Double Minute 2 Homolog Overexpression/alterations In mentioning

confidence: 99%

Section: Mouse Double Minute 2 Homolog Overexpression/alterations In mentioning

confidence: 99%

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Role of p53 Pathway Alterations in Uterine Carcinosarcomas (Malignant Mixed Müllerian Tumors)

et al. 2014

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In vitro effects of FBXW7 mutation in serous endometrial cancer: Increased levels of potentially druggable proteins and sensitivity to SI‐2 and dinaciclib

Urick

Bell

2018

Molecular Carcinogenesis

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Serous endometrial cancers (ECs) are clinically aggressive tumors that frequently harbor somatic mutations in FBXW7 (F-box and WD repeat domain-containing 7). The FBXW7 tumor suppressor is part of a SCF (complex of SKP1, Cullin 1, F-box protein) ubiquitin ligase complex which controls the degradation of numerous substrates that, if not properly regulated, can contribute to the initiation or progression of tumorigenesis. Despite reports that up to 30% of serous ECs include somatic mutations in FBXW7, the molecular effects of mutated FBXW7 in ECs have not been determined. Here, we used transient transfection and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) editing in serous EC cell lines to interrogate the molecular effects of six recurrent FBXW7 mutations. We show that FBXW7 mutations lead to increased Cyclin E1, steroid receptor coactivator 3 (SRC-3), c-MYC, Rictor, glycogen synthase kinase 3 (GSK3), P70S6 kinase, and protein kinase B (AKT) phosphorylated protein levels in serous EC cells. Furthermore, we demonstrate that CRISPR-edited FBXW7-mutant ARK1 serous EC cells exhibit increased sensitivity to SI-2 (a SRC inhibitor) and dinaciclib (a cyclin dependent kinase (CDK) inhibitor) compared to parental ARK1 cells. Collectively, our findings reveal biochemical effects of FBXW7 mutations in the context of EC and provide in vitro evidence of sensitivity to targeted inhibitors.

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Prognostic Factors in Uterine Cancer

Baker¹,

Oliva

2015

Current Clinical Oncology

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Malignant Mixed Müllerian Tumors of the Uterus: A Clinicopathologic, DNA Flow Cytometric, p53, and mdm-2 Analysis of 44 Cases

Cited by 32 publications

References 22 publications

Role of p53 Pathway Alterations in Uterine Carcinosarcomas (Malignant Mixed Müllerian Tumors)

Role of p53 Pathway Alterations in Uterine Carcinosarcomas (Malignant Mixed Müllerian Tumors)

In vitro effects of FBXW7 mutation in serous endometrial cancer: Increased levels of potentially druggable proteins and sensitivity to SI‐2 and dinaciclib

Prognostic Factors in Uterine Cancer

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