Scientific publications

Clinicopathological features and prognostic significance of CTNNB1 mutation in low-grade, early-stage endometrial endometrioid carcinoma

Dec 1, 2021 | Magazine: Virchows Archiv

Ignacio Ruz-Caracuel  1   2 , Álvaro López-Janeiro  1 , Victoria Heredia-Soto  3   4 , Jorge L Ramón-Patino  5   6 , Laura Yébenes  1   7 , Alberto Berjón  1   7 , Alicia Hernández  8   9 , Alejandro Gallego  4   5 , Patricia Ruiz  7 , Andrés Redondo  5   9 , Alberto Peláez-García  7 , Marta Mendiola  10   11 , David Hardisson  12   13   14   15


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.

CITATION  Virchows Arch. 2021 Dec;479(6):1167-1176.  doi: 10.1007/s00428-021-03176-5. Epub 2021 Aug 21.