scholarly journals Serous Carcinoma of the Endometrium with Mesonephric-Like Differentiation Initially Misdiagnosed as Uterine Mesonephric-Like Adenocarcinoma: A Case Report with Emphasis on the Immunostaining and the Identification of Splice Site TP53 Mutation

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 717
Author(s):  
Sangjoon Choi ◽  
Yoon Yang Jung ◽  
Hyun-Soo Kim
Keyword(s):  
Splice Site ◽  
Tp53 Mutation ◽  
Rare Condition ◽  
Growth Patterns ◽  
Serous Carcinoma ◽  
Wild Type ◽  
Gata3 Expression ◽  
Uterine Serous Carcinoma ◽  
P16 Expression ◽  
Viral Oncogene Homolog

We present herein a rare case of uterine serous carcinoma with mesonephric-like differentiation (SC-MLD) initially misdiagnosed as mesonephric-like adenocarcinoma (MLA). A 51-year-old woman underwent total hysterectomy for a uterine tumor. Histologically, the tumor exhibited various architectures, including papillary, glandular, tubular, cribriform, and cystic. On the basis of this architectural diversity accompanied by intraluminal eosinophilic secretions and intermediate-grade nuclear atypia, the initial diagnosis was MLA. However, the tumor was diffusely and strongly positive for the expression of p16 and negative for the expression of GATA-binding protein 3 (GATA3). Furthermore, we identified a pathogenic tumor protein 53 (TP53) mutation affecting an acceptor splice site in intron 9, despite a wild-type p53 immunostaining pattern. The observations of diffuse and strong p16 expression, lack of GATA3 expression, pathogenic TP53 mutation, and wild-type Kirsten rat sarcoma viral oncogene homolog indicate that this tumor was not an MLA but an SC-MLD. Both uterine SC and MLA can exhibit various histological growth patterns. Our comprehensive clinicopathological and molecular analyses can serve to improve the understanding of this rare condition and help pathologists in making an accurate diagnosis.

scholarly journals Uterine serous carcinoma: key advances and novel treatment approaches

2021 ◽  
pp. ijgc-2021-002753
Author(s):  
J Stuart Ferriss ◽  
Britt K Erickson ◽  
Ie-Ming Shih ◽  
Amanda N Fader
Keyword(s):  
Endometrial Cancer ◽  
Black Women ◽  
Treatment Options ◽  
Molecular Genetic ◽  
Serous Carcinoma ◽  
Cancer Syndrome ◽  
Her2 Positive ◽  
Incidence And Mortality ◽  
History Of ◽  
Uterine Serous Carcinoma

The incidence and mortality rates from endometrial cancer continue to increase worldwide, while rates in most other cancers have either plateaued or declined considerably. Uterine serous carcinoma represents a fraction of all endometrial malignancies each year, yet this histology is responsible for nearly 40% of all endometrial cancer-related deaths. These deaths disproportionately affect black women, who have higher rates of advanced disease at diagnosis. Molecular genetic analyses reveal major alterations including TP53 mutation, PIK3CA mutation/amplification, ERBB2 amplification, CCNE1 amplification, FBXW7 mutation/deletion, PPP2R1A mutation, and somatic mutations involving homologous recombination genes. Clinical risk factors for uterine serous carcinoma include advancing age, a history of breast cancer, tamoxifen usage, and the hereditary breast–ovarian cancer syndrome. Surgery remains the cornerstone of treatment. Recent advances in our understanding of uterine serous carcinoma molecular drivers have led to development of targeted therapeutics that promise improved outcomes for patients. Overexpression or amplification of HER2 in uterine serous carcinoma carries a poor prognosis; yet this actionable target has led to the incorporation of several anti-HER2 therapies, including trastuzumab which, when added to conventional chemotherapy, is associated with improved survival for women with advanced and recurrent HER2-positive disease. The combination of pembrolizumab and lenvatinib is also a promising targeted treatment strategy for women with uterine serous carcinoma, with a recent phase II study suggesting a 50% response rate in women with recurrent disease. Several trials examining additional targeted agents are ongoing. Despite years of stalled progress, meaningful, tailored treatment options are emerging for patients with this uncommon and biologically aggressive endometrial cancer subtype.

scholarly journals An MDM2 inhibitor achieves synergistic cytotoxic effects with adenoviruses lacking E1B55kDa gene on mesothelioma with the wild-type p53 through augmenting NFI expression

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Thao Thi Thanh Nguyen ◽  
Masato Shingyoji ◽  
Michiko Hanazono ◽  
Boya Zhong ◽  
Takao Morinaga ◽  
...  
Keyword(s):  
Wild Type ◽  
Inhibitory Effects ◽  
Cytotoxic Effects ◽  
P53 Expression ◽  
Nuclear Factor I ◽  
Infected Cells ◽  
Wild Type P53 ◽  
Mdm2 Inhibitor ◽  
P16 Expression

AbstractA majority of mesothelioma specimens were defective of p14 and p16 expression due to deletion of the INK4A/ARF region, and the p53 pathway was consequently inactivated by elevated MDM2 functions which facilitated p53 degradaton. We investigated a role of p53 elevation by MDM2 inhibitors, nutlin-3a and RG7112, in cytotoxicity of replication-competent adenoviruses (Ad) lacking the p53-binding E1B55kDa gene (Ad-delE1B). We found that a growth inhibition by p53-activating Ad-delE1B was irrelevant to p53 expression in the infected cells, but combination of Ad-delE1B and the MDM2 inhibitor produced synergistic inhibitory effects on mesothelioma with the wild-type but not mutated p53 genotype. The combination augmented p53 phosphorylation, activated apoptotic but not autophagic pathway, and enhanced DNA damage signals through ATM-Chk2 phosphorylation. The MDM2 inhibitors facilitated production of the Ad progenies through augmented expression of nuclear factor I (NFI), one of the transcriptional factors involved in Ad replications. Knocking down of p53 with siRNA did not increase the progeny production or the NFI expression. We also demonstrated anti-tumor effects by the combination of Ad-delE1B and the MDM2 inhibitors in an orthotopic animal model. These data collectively indicated that upregulation of wild-type p53 expression contributed to cytotoxicity by E1B55kDa-defective replicative Ad through NFI induction and suggested that replication-competent Ad together with augmented p53 levels was a therapeutic strategy for p53 wild-type mesothelioma.

Is platinum-free interval relevant in recurrent uterine serous carcinoma?

2020 ◽  
Vol 159 ◽  
pp. 205-206
Author(s):  
R.N. Beavers ◽  
B. Fellman ◽  
M. Eyada ◽  
A.H. Klopp ◽  
N.D. Fleming ◽  
...  
Keyword(s):  
Serous Carcinoma ◽  
Free Interval ◽  
Uterine Serous Carcinoma

Molecular Markers for Rapidly Identifying Candidate Genes in Chlamydomonas reinhardtii: ERY1 and ERY2 Encode Chloroplast Ribosomal Proteins

Genetics ◽  
2003 ◽  
Vol 164 (4) ◽  
pp. 1345-1353
Author(s):  
Amber K Bowers ◽  
Jennifer A Keller ◽  
Susan K Dutcher
Keyword(s):  
Molecular Markers ◽  
Chlamydomonas Reinhardtii ◽  
Candidate Genes ◽  
Splice Site ◽  
Genomic Dna ◽  
Ribosomal Proteins ◽  
Genomic Sequence ◽  
Point Mutations ◽  
Acceptor Site ◽  
Wild Type

Abstract To take advantage of available expressed sequence tags and genomic sequence, we have developed 64 PCR-based molecular markers in Chlamydomonas reinhardtii that map to the 17 linkage groups. These markers will allow the rapid association of a candidate gene sequence with previously identified mutations. As proof of principle, we have identified the genes encoded by the ERY1 and ERY2 loci. Mendelian mutations that confer resistance to erythromycin define three unlinked nuclear loci in C. reinhardtii. Candidate genes ribosomal protein L4 (RPL4) and L22 (RPL22) are tightly linked to the ERY1 locus and ERY2 locus, respectively. Genomic DNA for RPL4 from wild type and five mutant ery1 alleles was amplified and sequenced and three different point mutations were found. Two different glycine residues (G102 and G112) are replaced by aspartic acid and both are in the unstructured region of RPL4 that lines the peptide exit tunnel of the chloroplast ribosome. The other two alleles change a splice site acceptor site. Genomic DNA for RPL22 from wild type and three mutant ery2 alleles was amplified and sequenced and revealed three different point mutations. Two alleles have premature stop codons and one allele changes a splice site acceptor site.

scholarly journals P04.16 TP53 mutations in codon 273 is predictive of overall survival in astrocytoma patients

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii32-iii32
Author(s):  
H Noor ◽  
R Rapkins ◽  
K McDonald
Keyword(s):  
Overall Survival ◽  
Tp53 Mutation ◽  
Progression Free Survival ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Wild Type ◽  
Mutation Status ◽  
Free Survival ◽  
Tp53 Mutations ◽  
Fresh Frozen

Abstract BACKGROUND Tumour Protein 53 (TP53) is a tumour suppressor gene that is mutated in at least 50% of human malignancies. The prevalence of TP53 mutation is much higher in astrocytomas with reports of up to 75% TP53 mutant cases. Rare cases of TP53 mutation also exist in oligodendroglial tumours (10–13%). P53 pathway is therefore an important factor in low-grade glioma tumorigenesis. Although the prognostic impact of TP53 mutations has been studied previously, no concrete concordance were reached between the studies. In this study, we investigated the prognostic effects of TP53 mutation in astrocytoma and oligodendroglioma. MATERIAL AND METHODS A cohort of 65 matched primary and recurrent fresh frozen tumours were sequenced to identify hotspot exons of TP53 mutation. Exons 1 to 10 were sequenced and pathogenic mutations were mostly predominant between Exons 4 and 8. The cohort was further expanded with 78 low grade glioma fresh frozen tissues and hotspot exons were sequenced. Selecting only the primary tumour from 65 matched tumours, a total of 50 Astrocytoma cases and 51 oligodendroglioma cases were analysed for prognostic effects of TP53. Only pathogenic TP53 mutations confirmed through COSMIC and NCBI databases were included in the over survival and progression-free survival analysis. RESULTS 62% (31/50) of astrocytomas and 16% (8/51) of oligodendrogliomas harboured pathogenic TP53 mutations. Pathogenic hotspot mutations in codon 273 (c.817 C>T and c.818 G>A) was prevalent in astrocytoma with 58% (18/31) of tumours with these mutations. TP53 mutation status was maintained between primary and recurrent tumours in 93% of cases. In astrocytoma, overall survival of TP53 mutant patients was longer compared to TP53 wild-type patients (p<0.01) but was not significant after adjusting for age, gender, grade and IDH1 mutation status. In contrast, astrocytoma patients with specific TP53 mutation in codon 273 showed significantly better survival compared to other TP53 mutant and TP53 wild-type patients combined (p<0.01) in our multivariate analysis. Time to first recurrence (progression-free survival) of TP53 mutant patients was significantly longer than TP53 wild-type patients (p<0.01) after adjustments were made, while TP53 mutation in codon 273 was not prognostic for progression-free survival. In oligodendroglioma patients, TP53 mutations did not significantly affect overall survival and progression-free survival. CONCLUSION In agreement with others, TP53 mutation is more prevalent in Astrocytoma and mutations in codon 273 are significantly associated with longer survival.

Sign in / Sign up

Export Citation Format

Share Document