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Potential diagnostic biomarkers: differential expression of LMP2/β1i and cyclin B1 in human uterine leiomyosarcoma

Abstract

Aims and background. Whilst most uterine smooth muscle neoplasms are benign, uterine leiomyosarcoma (Ut-LMS) is extremely malignant with a high incidence of metastasis and recurrence. Gynecological tumors are often associated with female hormone secretion, but no strong link has been detected between human Ut-LMS and the hormonal environment. In fact, the risk factors for Ut-LMS are poorly understood. In addition, no diagnostic biomarkers for differentiating between leiomyoma, a benign tumor, and malignant Ut-LMS have been found. Interestingly, mice that were homozygously deficient for LMP2/β1i were found to spontaneously develop Ut-LMS and exhibited a Ut-LMS prevalence of ~40% by 14 months of age. Thus, analyzing potential risk factors for Ut-LMS (such as LMP2/β1i) might aid the development of diagnostic biomarkers and clinical treatments for the condition.
Methods and study design. Fifty-seven patients (age range: 32-83 years) who had been diagnosed with uterine mesenchymal tumors were chosen from a pathological archive. Tissue samples from these patients were fixed in 10% buffered formalin, incubated in 4% paraformaldehyde for 8 hours, and embedded in paraffin. Tissue sections were stained with hematoxylin and eosin for standard histological examination or were subjected to further processing for immunohistochemical (IHC) examination. Serial Ut-LMS, bizarre leiomyoma, leiomyoma, and myometrium sections were subjected to IHC staining of β-smooth muscle actin, estrogen receptor, cyclin B1, LMP2/β1i, calponin h1, ki-67, tumor protein p53, and progesterone receptor.
Results. The Ut-LMS samples were positive for cyclin B1 and negative for LMP2/β1i, while the opposite result was obtained for bizarre leiomyoma, leiomyoma, and myometrium samples.
Conclusions. The expression pattern of LMP2/β1i and cyclin B1 might be a diagnostic biomarker for human Ut-LMS. Studies of the biological roles of LMP2/β1i and/or cyclin B1 could lead to the elucidation of new targets for therapies against Ut-LMS.

Tumori 2014; 100(4): e99 - e106

Article Type: ORIGINAL RESEARCH ARTICLE

DOI:10.1700/1636.17918

Authors

Takuma Hayashi, Akiko Horiuchi, Kenji Sano, Nobuyoshi Hiraoka, Tomoyuki Ichimura, Tamotsu Sudo, Osamu Ishiko, Nobuo Yaegashi, Hiroyuki Aburatani, Ikuo Konishi

Article History

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Authors

  • Hayashi, Takuma [PubMed] [Google Scholar]
    Department of Immunology and Infectious Disease, Shinshu University Graduate School of Medicine, Matsumoto, Japan
  • Horiuchi, Akiko [PubMed] [Google Scholar]
    Horiuchi Ladies Clinic, Matsumoto, Japan
  • Sano, Kenji [PubMed] [Google Scholar]
    Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan
  • Hiraoka, Nobuyoshi [PubMed] [Google Scholar]
    Pathology Division, National Cancer Center Research Institute, Tokyo, Japan
  • Ichimura, Tomoyuki [PubMed] [Google Scholar]
    Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Sudo, Tamotsu [PubMed] [Google Scholar]
    Department of Gynecology, Hyogo Cancer Center, Hyogo, Japan
  • Ishiko, Osamu [PubMed] [Google Scholar]
    Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Yaegashi, Nobuo [PubMed] [Google Scholar]
    Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan
  • Aburatani, Hiroyuki [PubMed] [Google Scholar]
    The Cancer System Laboratory, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan
  • Konishi, Ikuo [PubMed] [Google Scholar]
    Department of Obstetrics and Gynecology, Kyoto University Graduate School of Medicine, Kyoto, Japan

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