Classification of high-grade endometrium carcinomas by molecular and immunohistochemical methods

Endometrial carcinomas are the 4th most common cancer in women, and the incidence is increasing. Some studies have shown that high-grade endometrial carcinomas have a very good prognosis and the classification based on morphological features has been shown to be insufficient. The most comprehensive molecular study for endometrial carcinomas.Endometrial carcinomas are classified into 4 groups according to their molecular and immunohistochemical properties; POLE ultramutated (Polymerase epsilon exonuclease domain mutation), MMR hypermutation (Mismatch repair mutation), Low copy number and high copy number groups. In our study, 17 patients with MMR (Mismatch repair) gene defect were firstly examined for Mismatch repair genes (MLH1, MSH2, MSH6, PMS2) by paraffin blocks of 56 high-grade endometrial cancer patients diagnosed at Akdeniz University Faculty of Medicine between 2005-2017. In order to detect POLE mutation in 39 patients without MMR gene defect, 10 hot spot mutations (P286R / S, V411L, F367S / C / L, P436R, A456P, L424P, E396Q) were evaluated in real-time PCR method. 31 patients without POLE mutations were immunohistochemically examined for p53.16 patients were included in the low copy number and 15 patients were included in the high number of copies. Later, clinical, histopathological features of these groups were compared. Overall survival and mean survival time were calculated. When the survival rates of the patients were compared according to the study groups, the overall survival rates of the patients with high copy number were found to be statistically lower than the patients with MMR hypermutation, POLE ultramutations and low copy number (p = 0.018; Log-rank test). There was no 78 statistically significant difference between tumor size, incidence of myometrial invasion, presence of LVI and stages according to study groups (p> 0.05). When the patients' ages were grouped as below 60 years and 60 years and above, it was found that the percentage of patients in the high copy number group was higher than the age of 60 and higher than the low number of copy group patients (p = 0.018). In the comparison of the study groups and histopathological features, many parameters could not be evaluated statistically because of the small number of cases. The number of such studies should be increased by providing more multicenter, more patients and sufficient financial resources.