Potential diagnostic biomarkers for human mesenchymal tumors, especially LMP2/b1i and cyclin E1 differential expression

Objectives: Most mesenchymal tumors found in the uterine corpus are benign tumors; however, uterine leiomyosarcoma is a malignant tumor with unknown risk factors that repeatedly recurs and metastasizes. In some cases, the histopathologic findings of uterine leiomyoma and uterine leiomyosarcoma are similar and surgical pathological diagnosis using excised tissue samples is difficult. It is necessary to analyze the risk factors for human uterine leiomyosarcoma and establish diagnostic biomarkers and treatments. Female mice deficient in the proteasome subunit low molecular mass peptide 2 (LMP2)/b1i develop uterine leiomyosarcoma spontaneously. Methodology: Out of 334 patients with suspected uterine mesenchymal tumors, patients diagnosed with smooth muscle tumors of the uterus were selected from the pathological file. To investigate the expression status of biomarker candidate factors, immunohistochemical staining was performed with antibodies of biomarker candidate factors on thin-cut slides of human uterine leiomyosarcoma, uterine leiomyoma, and other uterine mesenchymal tumors. Results: In human uterine leiomyosarcoma, there was a loss of LMP2/b1i expression and enhanced cyclin E1 and Ki-67 expression. In human uterine leiomyomas and normal uterine smooth muscle layers, enhanced LMP2/b1i expression and the disappearance of the expression of E1 and Ki-67 were noted. The pattern of expression of each factor in other uterine mesenchymal tumors was different from that of uterine leiomyosarcoma. Conclusions: LMP2/b1i, cyclin E1, and Ki-67 may be candidate factors for biomarkers of human uterine leiomyosarcoma. Further large-cohort clinical trials should be conducted to establish treatments and diagnostics for uterine mesenchymal tumors.