The incidence of endometrial cancer (EC) is increasing in developed countries. The most frequent is the endometrioid subtype with usually good prognosis; nevertheless, some cases escape this paradigm and may have recurrence. A recent study from The Cancer Genome Atlas suggested to implement the EC analysis by molecular profile for improving diagnosis, prognosis, and therapeutic treatment. The present preliminary study was performed on 15 G3 endometrioid endometrial cancers (G3 EEC) for the identification of somatic mutations in a panel of specific exons in selected genes as ARID1A, CTNNB1, KRAS, PIK3CA, POLE, PTEN, and TP53. The combined procedure, based on the Sanger sequencing and PCR-high-resolution melting analysis, allowed the identification of variations of the selected gene panel in most of patients (93%) of our cohort. The overall evaluation of mutational load exhibited that the most frequent mutated genes were PTEN (93%), followed by PIK3CA (47%) suggesting a deep involvement of PI3K pathway alteration in G3 EEC. Mutations in TP53 (27%), ARID1A (27%), POLE (13%), and at the lower level in KRAS and CTNNB1 (7%) were also observed (exclusively in FIGO III stage patients). The evaluation of the mutations of our proposed panel (ARID1A, CTNNB1, KRAS, PIK3CA, POLE, PTEN, TP53) is suitable to improve the characterization of G3 EEC and could suggest targetable pathways for development of personalized treatments.
Keywords: Combined PCR-high resolution melting analysis (PCR-HRMA) and Sanger sequencing; Endometrioid endometrial cancer; Grade 3 EEC; Mutational load; Somatic mutations.