Low-Grade Endometrial Cancer with Abnormal p53 Expression as a Separate Clinical Entity: Insights from RNA Sequencing and Immunohistochemistry

Background: A molecular classification of endometrial cancer was developed based on an analysis of The Cancer Genome Atlas. In this classification, the group characterized by abnormal p53 immunohistochemical expression showed the poorest prognosis. However, there may be no need to apply a molecular classification in low-grade endometrial cancer. In this study, we investigated the clinical significance of abnormal p53 immunohistochemical expression in low-grade endometrial cancer. Methods: We obtained nine frozen samples of endometrial cancer [low-grade endometrial cancer with wild-type p53 expression (EC^lop53^wt group): n = 3, low-grade endometrial cancer with abnormal p53 expression (EC^lop53^ab group): n = 3, and high-grade endometrial cancer (EC^hi group): n = 3]. RNA sequencing was performed for each sample. All the samples passed RNA quality control. In addition, an immunohistochemical analysis was performed for 44 formalin-fixed paraffin-embedded samples. Results: Differentially expressed genes were identified in the RNA sequencing results (1811 genes between the EC^lop53^ab group and the EC^hi group, and 1088 genes between the EC^lop53^ab group and the EC^lop53^wt group). In a principal component analysis, the EC^lop53^ab group was more similar to the EC^lop53^wt group than to the EC^hi group. In the immunohistochemical analysis, L1CAM expression was significantly less frequently observed in the EC^lop53^ab group than in the EC^hi group. Moreover, p21 expression tended to be more frequently observed in the EC^lop53^ab group than in the EC^hi group. Conclusions: In this study, the RNA sequencing and immunohistochemical results revealed that the EC^lop53^ab group is a separate entity from the EC^hi group. While the abnormal p53 group is considered the most prognostically unfavorable in molecular classification, these findings suggest that routine molecular profiling is not necessary for patients with low-grade endometrial cancer. However, there is insufficient evidence to modify adjuvant treatment in low-grade endometrial cancer patients. Further investigation is needed on the clinical application of molecular classification to low-grade endometrial cancer.