title: Potential diagnostic biomarkers: differential expression of LMP2/β1i and cyclin B1 in human uterine leiomyosarcoma.
abstract: OBJECTIVE
  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
  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.
authors.forename: Takuma
authors.initials: T
authors.lastname: Hayashi
authors.forename: Akiko
authors.initials: A
authors.lastname: Horiuchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sano
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hiraoka
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ichimura
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sudo
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishiko
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D056744:Cyclin B1 / Q000032:analysis*; D003546:Cysteine Endopeptidases / Q000032:analysis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000175:diagnosis; D007890:Leiomyosarcoma / Q000737:chemistry / Q000175:diagnosis* / Q000473:pathology; D008875:Middle Aged; D009215:Myometrium / Q000737:chemistry; D009367:Neoplasm Staging; D014594:Uterine Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D056744:Cyclin B1; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases