Involvement of proteasome β1i subunit, LMP2, on development of uterin leiomyosarcma

Takuma Hayashi; Akiko Horiuchi; Kenji Sano; Nobuyoshi Hiraoka; Mari Kasai; Tomoyuki Ichimura; Satoru Nagase; Osamu Ishiko; Tanri Shiozawa; Yae Kanai; Nobuo Yaegashi; Hiroyuki Aburatani; Susumu Tonegawa; Ikuo Konishi

doi:10.4297/najms.2011.3394

Involvement of proteasome β1i subunit, LMP2, on development of uterin leiomyosarcma

N Am J Med Sci. 2011 Sep;3(9):394-9. doi: 10.4297/najms.2011.3394.

Authors

Takuma Hayashi¹, Akiko Horiuchi, Kenji Sano, Nobuyoshi Hiraoka, Mari Kasai, Tomoyuki Ichimura, Satoru Nagase, Osamu Ishiko, Tanri Shiozawa, Yae Kanai, Nobuo Yaegashi, Hiroyuki Aburatani, Susumu Tonegawa, Ikuo Konishi

Affiliation

¹ Department of Immunology and Infectious Disease, Shinshu University Graduate School of Medicine, Japan.

Abstract

Background: Although the majority of smooth muscle neoplasms found in the uterus are benign, uterine leiomyosarcoma is extremely malignant, with high rates of recurrence and metastasis. The development of gynecologic tumors is often correlated with secretion of female hormone; however, the development of human uterine leiomyosarcoma is not substantially correlated with hormonal conditions, and the risk factors are unclearly understood. Importantly, a diagnostic-biomarker, which distinguishes malignant human uterine leiomyosarcoma from benign tumor leiomyoma is yet to be established.

Aims: It is necessary to analyze risk factors associated with human uterine leiomyosarcoma, in order to establish a diagnostic-biomarker and a clinical treatment method.

Patients and methods: HISTOLOGY AND IMMUNOFLUORESCENCE STAINING: Uteri obtained from LMP2(-/-) mice or its parental mice (C57BL/6 mice) were fixed in 10% buffered formalin, incubated in 4% paraformaldehyde for 8 hours, and embedded in paraffin. Tissue sections (5 μm) were prepared and stained with H&E for routine histological examination or were processed further for immunofluorescence staining with appropriate antidodies. Furthermore, a total of 101 patients between 32 and 83 years of age and diagnosed as having smooth muscle tumors of the uterus were selected from pathological files. Immunohistochemistry staining for LMP2 was performed on serial human uterine leiomyosarcoma, leiomyoma and myometrium sections.

Results: Homozygous deficient mice for a proteasome β1i subunit, LMP2 spontaneously develop uterine leiomyosarcoma, with a disease prevalence of ~40% by 14 months of age. Defective LMP2 expression in human uterine leiomyosarcoma was demonstrated, but present in human leiomyoma and myometrium.

Conclusions: Loss in LMP2 expression may be one of the risk factors for human uterine leiomyosarcoma. LMP2 may be a potential diagnostic-biomarker and targeted-molecule for a new therapeutic approach.

Keywords: LMP2; diagnostic-biomarker; uterine leiomyoma; uterine leiomyosarcoma.