Recommendations for biomarker testing in epithelial ovarian cancer: a National Consensus Statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology

Oaknin, Ana; Guarch, Rosa; Barretina-Ginesta, Maria-Pilar; Hardisson, David; González-Martín, Antonio; Matías‐Guiu, Xavier; Fidalgo, José Alejandro Pérez; Vieites, Begoña; Romero, Ignacio; Palacios, José

doi:10.1007/s12094-017-1719-x

Cited by 7 publications

(8 citation statements)

References 73 publications

(77 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…WT1 is not expressed in the epithelium of healthy fallopian tubes, which is assumed to be the site of origin of most HGSOC [38], and it is a recognized marker of serous differentiation, useful to distinguish serous tumors (both high-grade from low-grade) from other tumor types [39]. Diffuse p16 staining supports a diagnosis of HGSOC, especially when p53 expression is uncertain [40]. The prognostic value of WT1 expression marker has been also investigated in HGSOC, but with opposite effects [38,41].…”

Section: Discussionmentioning

confidence: 99%

Clonal Evolution of TP53 c.375+1G>A Mutation in Pre- and Post- Neo-Adjuvant Chemotherapy (NACT) Tumor Samples in High-Grade Serous Ovarian Cancer (HGSOC)

Garziera

Cecchin

Giorda

et al. 2019

Cells

View full text Add to dashboard Cite

Carboplatin/paclitaxel is the reference regimen in the treatment of advanced high-grade serous ovarian cancer (HGSOC) in neo-adjuvant chemotherapy (NACT) before interval debulking surgery (IDS). To identify new genetic markers of platinum-resistance, next-generation sequencing (NGS) analysis of 26 cancer-genes was performed on paired matched pre- and post-NACT tumor and blood samples in a patient with stage IV HGSOC treated with NACT-IDS, showing platinum-refractory/resistance and poor prognosis. Only the TP53 c.375+1G>A somatic mutation was identified in both tumor samples. This variant, associated with aberrant splicing, was in trans configuration with the 72Arg allele of the known germline polymorphism TP53 c.215C>G (p. Pro72Arg). In the post-NACT tumor sample we observed the complete expansion of the TP53 c.375+1G>A driver mutant clone with somatic loss of the treatment-sensitive 72Arg allele. NGS results were confirmed with Sanger method and immunostaining for p53, BRCA1, p16, WT1, and Ki-67 markers were evaluated. This study showed that (i) the splice mutation in TP53 was present as an early driver mutation at diagnosis; (ii) the mutational profile was shared in pre- and post-NACT tumor samples; (iii) the complete expansion of a single dominant mutant clone through loss of heterozygosity (LOH) had occurred, suggesting a possible mechanism of platinum-resistance in HGSOC under the pressure of NACT.

show abstract

Section: Discussionmentioning

confidence: 99%

Clonal Evolution of TP53 c.375+1G>A Mutation in Pre- and Post- Neo-Adjuvant Chemotherapy (NACT) Tumor Samples in High-Grade Serous Ovarian Cancer (HGSOC)

Garziera

Cecchin

Giorda

et al. 2019

Cells

View full text Add to dashboard Cite

show abstract

“…Common hub DEGs were marked red vast majority of ovarian cancers are epithelial ovarian cancers which accounts for over 95% of the ovarian malignancies, and about 75% of epithelial ovarian cancers are serous type. Moreover, high-grade serous epithelial ovarian cancer is the most common subtype and accounts for up to 70% of all ovarian cancer cases [29], it is associated with worse outcomes including poor prognosis and a high risk of distant recurrence and death [30]. Hence, ovarian carcinomas of the serous histological type are an attractive target for early detection as they are rarely detected before they reach an advanced stage, when they are highly lethal.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of gene expression profile of serous ovarian carcinomas to screen key genes and pathways

Fei

Chen

2020

J Ovarian Res

View full text Add to dashboard Cite

Background: Serous ovarian carcinomas (SCA) are the most common and most aggressive ovarian carcinoma subtype which etiology remains unclear. To investigate the prospective role of mRNAs in the tumorigenesis and progression of SCA, the aberrantly expressed mRNAs were calculated based on the NCBI-GEO RNA-seq data. Results: Of 21,755 genes with 89 SCA and SBOT cases from 3 independent laboratories, 59 mRNAs were identified as differentially expressed genes (DEGs) (|log 2 Fold Change| > 1.585, also |FoldChange| > 3 and adjusted P < 0.05) by DESeq R. There were 26 up-regulated DEGs and 33 down-regulated DEGs screened. The hierarchical clustering analysis, functional analysis and pathway enrichment analysis were performed on all DEGs and found that Polo-like kinase (PLK) signaling events are important. PPI network constructed with different filtration conditions screened out 4 common hub genes (KIF11, CDC20, PBK and TOP2A). Mutual exclusivity or co-occurrence analysis of 4 hub genes identified a tendency towards co-occurrence between KIF11 and CDC20 or TOP2A in SCA (p < 0.05). To analyze further the potential role of KIF11 in SCA, the co-expression profiles of KIF11 in SCA were identified and we found that CDC20 co-expressed with KIF11 also is DEG that we screened out before. To verify our previous results in this paper, we assessed the expression levels of 4 hub DEGs (all up-regulated) and 4 down-regulated DEGs in Oncomine database. And the results were consistent with previous conclusions obtained from GEO series. The survival curves showed that KIF11, CDC20 and TOP2A expression are significantly related to prognosis of SCA patients. Conclusions: From all the above results, we speculate that KIF11, CDC20 and TOP2A played an important role in SCA.

show abstract

“…Immunohistochemical staining for p53 was used as a surrogate for TP53 mutational analysis to discriminate between high (over 96% was mutated) and low-grade serous carcinomas [17][18][19][20] . In the present study, p53 positivity was observed in 35.1% (40/114) of EOC cases, and higher positivity was showed in HGS (53.7%; 29/54); a significant association was found between p53 expression and histopathological diagnosis and with tumor grade and tumor type.…”

Section: Discussionmentioning

confidence: 99%

“…The differences found between the studies in the frequency of p53 expression may be due to the differences in scoring of p53 expression and interpretation of results: some studies scored this as overexpression (OE), complete absence (CA), cytoplasmic (CY) or normal/wild type (WT) 18,20 . Some authors consider complete absence of p53 expression as a mutant also because not all TP53 mutations alter the expression of the protein 15,17,25 . Complete absence of p53 expression does not indicate TP53 mutation, as a lack of immunoexpression may be found in normal cells 16 .…”

Section: Discussionmentioning

confidence: 99%

“…Immunohistochemical staining for p53 was considered as an essential biomarker for clinical trials targeting mutant p53 and used in the diagnostic workup of carcinomas of multiple sites, including ovarian cancers 16 . It is used as a substitute for TP53 mutational analysis, these mutations were global in high-grade serous ovarian cancer (HGSOC) (over 96% were mutated), so were used to discriminates between high-and lowgrade serous carcinomas [17][18][19][20] . Access to TP53 sequencing is not feasible in many low-and middle-income countries; pathologists there used p53 immunohistochemistry, which is quick, easy to perform, inexpensive and can approach 100% specificity for the presence of TP53 mutation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Immunohistochemical expression of p53 in Type I and II epithelial ovarian cancer among Sudanese women: a cross-sectional study

et al. 2019

View full text Add to dashboard Cite

Background: Epithelial ovarian cancer (EOC) represents the leading cause of death from gynecologic malignancies worldwide. In Sudan, ovarian cancer represents the fourth most frequent tumors among females. TP53 somatic mutations is a defining feature of ovarian high-grade serous carcinoma. However, p53 sequencing is not feasible in most low- and middle-income countries, like Sudan, and its frequency varies greatly. The study aimed to determine the frequency of p53 overexpression and its relationship with tumor types I and II and tumor grade among Sudanese women with EOC. Methods: In this cross-sectional, hospital-based study a total of 114 paraffin-embedded tissue blocks previously diagnosed as epithelial ovarian cancer were collected from six governmental hospitals in Khartoum state, Sudan, in the period 2013-2016. Immunohistochemistry was performed on tissue microarray slides to measure the protein expression of p53 in the EOC. Results: Overexpression of p53 was detected in 35.1% (n=40/114) of EOC samples, with a higher frequency in women with Type II 53.7% (n= 29/54) than type I 18.5% (n= 10/54) (P= 0.000). Also, a high frequency of p53 overexpression was evident in 49.2% (n= 30/61) of high-grade carcinoma compared with 16.7% (n= 1/6) of non-graded borderline tumors, and in 19.1% (n= 9/47) of low-grade tumors (P= 0.003). A high-grade serous carcinoma harbor p53 overexpression in 53.7% (n= 29/54) and none of low-grade serous carcinoma harbor p53 overexpression. Our result showed a significant association between p53 overexpression and tumor types and grades (P = 0.000 and 0.003, respectively) Conclusion: p53 over-expression was detected in one-third of Sudanese women with EOC. It was more common in type II EOC and high-grade serous, but negative in low-grade serous tumors. Our result showed a significant association between p53 over-expression and tumor type and grade, and can help discriminate between high- and low-grade serous carcinomas.

show abstract

Recommendations for biomarker testing in epithelial ovarian cancer: a National Consensus Statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology

Cited by 7 publications

References 73 publications

Clonal Evolution of TP53 c.375+1G>A Mutation in Pre- and Post- Neo-Adjuvant Chemotherapy (NACT) Tumor Samples in High-Grade Serous Ovarian Cancer (HGSOC)

Clonal Evolution of TP53 c.375+1G>A Mutation in Pre- and Post- Neo-Adjuvant Chemotherapy (NACT) Tumor Samples in High-Grade Serous Ovarian Cancer (HGSOC)

Bioinformatics analysis of gene expression profile of serous ovarian carcinomas to screen key genes and pathways

Immunohistochemical expression of p53 in Type I and II epithelial ovarian cancer among Sudanese women: a cross-sectional study

Contact Info

Product

Resources

About