Molecular mechanisms of uterine leiomyosarcomas: involvement of defect in LMP2 expression.
Patients with uterine leiomyosarcoma (LMS) typically present with vaginal bleeding, pain, and a pelvic mass. Typical presentations with hypercalcemia or eosinophilia have been reported. Radiographic evaluation with combined positron emission tomography/computed tomography may assist in the diagnosis and surveillance of women with uterine LMS. A recently developed risk-assessment index is highly predictive of disease-specific survival. Ovarian preservation does not appear to negatively impact outcome, and the addition of adjuvant therapy after surgical treatment does not seem to improve survival. It is noteworthy that LMP2-deficient mice exhibit spontaneous development of uterine LMS with a disease prevalence of approximately 37% by 12 months of age. The LMP2 gene is transcribed from a promoter containing an interferon (IFN)-gamma-response factor element; thus, the IFN-gamma-signal strongly induces LMP2 expression. Furthermore, a recent report demonstrated the loss of ability to induce LMP2 expression, which is an interferon (IFN)-gamma-inducible factor, in human uterine LMS tissues and cell lines. Analysis of human uterine LMS shows somatic mutations in the IFN gamma signalling pathway, thus the loss of LMP2 induction is attributable to a defect in the earliest steps of the IFN-gamma signalling pathway. The discovery of an impaired key cell-signalling pathway may provide new targets for diagnostic approaches and therapeutic intervention.
Department of Immunology and Infectious Disease, Shinshu University Graduate School of Medicine, Nagano, Japan. takuma-h@sch.md.shinshu-u.ac.jp
Takuma
T
Hayashi
Yuto
Y
Shimamura
Taro
T
Saegusa
Akiko
A
Horiuchi
Yukihiro
Y
Kobayashi
Nobuyoshi
N
Hiraoka
Yae
Y
Kanai
Hiroyuki
H
Aburatani
Kenji
K
Sano
Ikuo
I
Konishi