Clinicopathological features and prognostic significance of CTNNB1 mutation in low-grade, early-stage endometrial endometrioid carcinoma
| Autor: | Ignacio Ruz-Caracuel, Patricia Ruiz, Andrés Redondo, Álvaro López-Janeiro, Laura Yébenes, Alejandro Gallego, Victoria Heredia-Soto, Jorge L Ramón-Patino, Alberto Berjón, David Hardisson, Marta Mendiola, Alicia Hernández, Alberto Peláez-García |
|---|---|
| Přispěvatelé: | UAM. Departamento de Anatomía Patológica |
| Rok vydání: | 2021 |
| Předmět: |
Lymphoid Enhancer-Binding Factor 1
Medicina DNA Mutational Analysis Risk Assessment Disease-Free Survival Pathology and Forensic Medicine Exon Endometrial cancer Risk Factors Biomarkers Tumor medicine PMS2 Humans LEF1 CTNNB1 mutation Molecular Biology beta Catenin Aged Neoplasm Staging Retrospective Studies Tissue microarray business.industry Endometrioid carcinoma Microsatellite instability Exons Cell Biology General Medicine Low grade Middle Aged medicine.disease Prognosis Immunohistochemistry Endometrial Neoplasms MSH6 MSH2 Beta-catenin Mutation Mutation (genetic algorithm) Cancer research Female Original Article Neoplasm Grading Neoplasm Recurrence Local business Carcinoma Endometrioid |
| Zdroj: | Biblos-e Archivo. Repositorio Institucional de la UAM instname Virchows Archiv |
| Popis: | Low-grade and early-stage endometrioid endometrial carcinomas (EECs) have an overall good prognosis but biomarkers identifying patients at risk of relapse are still lacking. Recently, CTNNB1 exon 3 mutation has been identified as a potential risk factor of recurrence in these patients. We evaluate the prognostic value of CTNNB1 mutation in a single-centre cohort of 218 low-grade, early-stage EECs, and the correlation with beta-catenin and LEF1 immunohistochemistry as candidate surrogate markers. CTNNB1 exon 3 hotspot mutations were evaluated by Sanger sequencing. Immunohistochemical staining of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6), p53, beta-catenin, and LEF1 was performed in representative tissue microarrays. Tumours were also reviewed for mucinous and squamous differentiation, and MELF pattern. Nineteen (8.7%) tumours harboured a mutation in CTNNB1 exon 3. Nuclear beta-catenin and LEF1 were significantly associated with CTNNB1 mutation, showing nuclear beta-catenin a better specificity and positive predictive value for CTNNB1 mutation. Tumours with CTNNB1 exon 3 mutation were associated with reduced disease-free survival (p = 0.010), but no impact on overall survival was found (p = 0.807). The risk of relapse in tumours with CTNNB1 exon 3 mutation was independent of FIGO stage, tumour grade, mismatch repair protein expression, or the presence of lymphovascular space invasion. CTNNB1 exon 3 mutation has a negative impact on disease-free survival in low-grade, early-stage EECs. Nuclear beta-catenin shows a higher positive predictive value than LEF1 for CTNNB1 exon 3 mutation in these tumours This research was funded by the Instituto de Salud Carlos III (ISCIII) (PI17/01723), co-financed by the European Development Regional Fund ‘A way to achieve Europe’ (FEDER) |
| Databáze: | OpenAIRE |
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