Association of immunohistochemical pole, mismatch repair (MMR) andp53 mutations with myometrial invasion in figo grade 1 endometrioidtype endometrial carcinoma

Endometrial cancer (EC) is one of the most common gynecological tumors. According to the GLOBOCAN 2020 database of the Global Cancer Observatory (GCO), part of the International Agency for Research on Cancer (IARC), endometrial cancer is the sixth most commonly diagnosed cancer in women, accounting for 417.000 new cases and 97.000 deaths, or 4.5% of all tumors in women. The global incidence of endometrial cancer continues to rise, unlike many other cancers where incidence rates have declined over the past two decades. The first subtype classification of endometrial cancer was made by Bokhman in 1983 as Type I and Type II endometrial cancer based on clinical and hormonal characteristics. In 2013, The Cancer Genome Atlas (TCGA) showed that EC's can be divided into four groups based on integrated molecular characterization, mutational burden and somatic copy number variations. These 4 subgroups are POLE ultra mutation, mismatch repair deficiency (MMRd), P53 mutation (p53abn) and carcinoma without specific molecular profile (p53 wild type-p53wt). In our study, cases diagnosed as grade 1 endometrioid type endometrial carcinoma at the Department of Medical Pathology, Meram Faculty of Medicine were re-evaluated. POLE, P53, MMR (MLH-1, MSH-2, MSH-6, PMS2) staining was performed by immunohistochemistry. Data were statistically compared with clinicopathologic parameters. There was a statistically significant difference between p53 final score results and MMRp/MMRd groups (p=0.005). In 21 cases with negative p53 final score, no loss of expression of any of the MMR proteins was observed. Of the 50 cases in our study, 40% (n=20) were in the MMRd group and 60% in the MMRp group (n=30). Among the 20 cases in the MMRd group, 75% (n=15) had loss of MLH-1 and PMS-2 expression, 15% (n=3) had loss of MSH-2 and MSH-6 expression, and 5% (n=1) had loss of PMS-2 and MSH-6 expression only. Among clinical and histopathologic parameters, there was a low positive correlation between age and myometrial invasion (r=0.373, p=0.008). There was a moderate positive correlation between lymph node metastasis and adnexal involvement (r=0.484, p=0.00), a strong positive correlation between stage and myometrial invasion (r=0.818, p=0.00), a moderate positive correlation with stage and lower uterine segment involvement, and a significant positive correlation with cervical involvement (r values r=0.520 r=0.664; p values p=0.00 p=0.00, respectively). We believe that subtyping of endometrial cancer according to immunohistochemical POLE, p53 and MMR expression is important for planning surgical, adjuvant and targeted therapies.