Integrating Pathology, Chromosomal Instability and Mutations for Risk Stratification in Early-stage Endometrioid Endometrial Carcinoma

Li, Yuan; Li, Jiaqi; Guo, Ensong; Huang, Jia; Fang, Guangguang; Chen, Shaohua; Yang, Bin; Yu, Fu; Li, Fuxia; Wang, Zizhuo; Xiao, Rourou; Liu, Chen; Huang, Yuhan; Wu, Xiao Qing; Lü, Fang; You, Lixin; Feng, Ling; Xi, Ling; Wu, Peng; Ma, Ding; Sun, Chaoyang; Wang, Beibei; Chen, Gang

doi:10.21203/rs.3.rs-58862/v2

Cited by 4 publications

(8 citation statements)

References 37 publications

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“…On the other hand, the association between CTNNB1 mutation and decreased DFS was not significant, although it became significant after excluding cases with known molecular status other than NSMP. Five out of seven included studies only included low-grade EC, which mostly fall into the NSMP subgroup, although individual studies also showed a significant prognostic value for CTNNB1 mutation in subsets of high-grade EC [ 16 ]. These findings support that CTNNB1 mutation may be a valuable marker for identifying early stage endometrioid EC which have increased risk of recurrence and need an adjuvant treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Seven studies with a total sample size of 1031 patients with early-stage endometrioid EC were included [11][12][13][14][15][16][17]. The process of study selection is shown in Fig.…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

“…Therefore, the biological behavior of ECs within this group might be affected by other molecular features which are not considered in the TCGA classification. In recent years, several studies proposed that mutations in the exon 3 of CTNNB1 (β-catenin-encoding gene) could identify low-grade, early stage endometrioid EC at increased risk of recurrence [12][13][14][15][16]. This would be of paramount importance for the patient management, in terms of choice of appropriate adjuvant treatment.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis

Travaglino

Raffone

Raimondo

et al. 2022

Arch Gynecol Obstet

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Background In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP). Objective To define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis. Methods Electronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I–II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value < 0.05. Results Seven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026). Conclusion CTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.

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Section: Discussionmentioning

confidence: 99%

“…Seven studies with a total sample size of 1031 patients with early-stage endometrioid EC were included [11][12][13][14][15][16][17]. The process of study selection is shown in Fig.…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis

Travaglino

Raffone

Raimondo

et al. 2022

Arch Gynecol Obstet

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“…e risk stratification of UCEC based on the molecular subtypes was the prerequisite for prognostic evaluation. However, it was far from optimizing the treatment guidelines [3]. Further studies are needed to explore suitable biomarkers for purpose of developing more effective treatments and improving the outcome for patients.…”

Section: Introductionmentioning

confidence: 99%

ASPM, CDC20, DLGAP5, BUB1B, CDCA8, and NCAPG May Serve as Diagnostic and Prognostic Biomarkers in Endometrial Carcinoma

2022

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Uterine Corpus Endometrial Carcinoma (UCEC), the most common gynecologic malignancy in developed countries, remains to be a major public health problem. Further studies are surely needed to elucidate the tumorigenesis of UCEC. Herein, intersecting 203 differentially expressed genes (DEGs) were identified with the GSE17025, GSE63678, and e Cancer Genome Atlas-UCEC datasets. e Gene Ontology/Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis and protein-protein interaction (PPI) network were performed on those 203 DEGs. Intriguingly, 6 of the top 10 nodes in the PPI network were related to unfavorable prognosis, that is, ASPM, CDC20, DLGAP5, BUB1B, CDCA8, and NCAPG. e mRNA and protein expression levels of the 6 hub genes were elevated in UCEC tissues compared to normal tissues. Higher expression of the 6 hub genes was associated with poor prognostic clinicopathological characteristics. e receiver operating characteristic curve suggested the significant diagnostic ability of the 6 hub genes for UCEC. en, underlying pathogeneses of UCEC including promoter methylation level, TP53 mutation status, genomic genetic variation, and immune cells infiltration were analyzed. e mRNA expression level of the 6 hub genes was also higher in cervical squamous cell carcinoma and endocervical adenocarcinoma, uterine carcinosarcoma, and ovarian serous cystadenocarcinoma tissues than in corresponding normal tissues. In conclusion, ASPM, CDC20, DLGAP5, BUB1B, CDCA8, and NCAPG may be considered diagnostic and prognostic biomarkers in UCEC.

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“…Therefore, the enhancement of the molecular classification system will improve routine pathologic practice and enhance early diagnostic approaches. 4 Recently, the genetic and molecular basis of EC classification has gained much importance; with mutationtype p53 being the worst prognosis. Genetic analysis is expensive and requires specialized laboratories.…”

mentioning

confidence: 99%

p53, Pirh2, and L1CAM as Promising Prognostic Biomarkers of Endometrial Carcinoma: An Immunohistochemical and Genetic Study

Abdelrahman¹,

Salem²,

Attar

et al. 2022

Applied Immunohistochemistry &Amp; Molecular Morphology

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Endometrial cancer (EC) is the most common gynecologic cancer and the current methods for the prediction of its prognosis and treatment response are unfortunately suboptimal. In this study, we evaluated the prognostic value of p53, Pirh2, and L1CAM in 60 cases of EC using immunohistochemistry (IHC) and polymerase chain reaction. TP53 missense mutations result in nuclear accumulation of p53 protein that can be detected as overexpression by IHC. This is in the form of diffuse strong nuclear positivity involving at least at least >50% of the tumor cells as a whole or if >50% of the tumor cells of a discrete geographical areas. Abnormal p53 IHC expression was expressed in 33.3% of the cases and significantly associated with the tumor grade, myometrial invasion (MI), lymphovascular invasion (LVSI), nodal metastasis, and FIGO stage, and the advanced European Society for Medical Oncology (ESMO) risk groups (P<0.001 for each). High IHC Pirh2 expression was noted in 58.3% of the cases, and significantly associated with MI, LVSI, nodal metastasis, FIGO stage, and high-risk group (P<0.001, P=0.011, P=0.010, P=0.024, P=0.005, respectively). There was a significant upregulation of Pirh2 mRNA expression in EC specimens as compared with the control adjacent tissues (P=0.001). Upregulated Pirh2 mRNA expression had a significant association with Pirh2 immunostaining, tumor grade, tumor stage, MI, lymph node involvement, LVSI, and relapse (P<0.001 for each). Positive L1CAM immunoexpression was noted in 26.7% and was significantly associated with grade, MI, LVSI, nodal metastasis, FIGO stage, and high-risk group (P=0.003, P=0.023, P=0.003, P<0.001, P<0.001, P=0.002, respectively). Analysis of follow-up period revealed that EC with abnormal p53 IHC expression, high pirh2 and positive L1CAM expression exhibited a potent relation with tumor relapse, shorter overall survival and disease-specific survival (P<0.001 for each). Mutant p53, high Pirh2, and L1CAM-positive EC are highly aggressive tumors with a shortened survival rate, dismal outcome, and high risk of relapse after the standard protocol of therapy.

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Integrating Pathology, Chromosomal Instability and Mutations for Risk Stratification in Early-stage Endometrioid Endometrial Carcinoma

Cited by 4 publications

References 37 publications

Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis

Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis

ASPM, CDC20, DLGAP5, BUB1B, CDCA8, and NCAPG May Serve as Diagnostic and Prognostic Biomarkers in Endometrial Carcinoma

p53, Pirh2, and L1CAM as Promising Prognostic Biomarkers of Endometrial Carcinoma: An Immunohistochemical and Genetic Study

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