Histopathological and molecular findings in 98 cases of endometrial carcinoma: MMR, p53 and next generation sequencing.

Abstract

Gynecological malignancies arise from hereditary and somatic mutations, transcriptional aberrations, and genomic alterations influenced by epigenetic factors. This study aims to identify the mutations and their frequency in endometrial carcinomas (EC), and furthermore, to determine the relationship of these mutations with histopathological and immunohistochemical (IHC) parameters. The study was carried out in a retrospective cohort of 98 patients who received treatment upon being diagnosed with EC at a tertiary university hospital in Turkey between 2016 and 2021. The NGS-DNA tumor panel containing 29 genes was used in the study. NGS data of the cases were obtained from state of the evidence Tier 1 and 2 mutations. The relationship of patients' next generation sequencing (NGS) DNA panel results with histopathological parameters and IHC results (MLH1, MSH2, PMS2, MSH6 and p53) were evaluated. In 59 of the 98 cases, mutations were detected in at least one gene investigated with the NGS DNA panel. The most common somatic mutations in endometrial carcinoma were PIK3CA (33.6%), CTNNB1 (16.3%), KRAS (12.2%) and FGFR2 (11.2%) in this cohort. Abnormal p53 was detected by IHC in 15 out of 75 (20%) cases. Loss of expression was observed in at least one mismatch repair (MMR) protein by means of IHC in 39 out of 72 (39.8%) cases. Metastasis was found in 14 out of 82 (14.3%) patients who underwent lymph node dissection. FGFR2 mutation was more common in the group with lymph node metastasis compared to those without metastasis (p=0.02). We report the mutational landscape of EC in a tertiary referral hospital in northwestern Turkey. Although our data are very limited, we think that the FGFR2 mutation may be associated with lymph node metastasis, but studies with larger patient numbers and longer follow-up periods are needed.