Involvement of cyclins in cell proliferation and their clinical implications in soft tissue smooth muscle tumors.
Expression of cyclins A and E and cyclin-dependent kinase 2 (cdk2) was examined immunohistochemically in 55 cases of soft tissue smooth muscle tumors, including vascular leiomyoma, and compared to expression of Ki-67 and proliferating cell nuclear antigen. Cyclin A was expressed in 70% of the leiomyoma cases, but with much lower labeling indexes than in leiomyosarcoma. Cyclin E was expressed exclusively in leiomyosarcoma. Although the differences of cyclin A- and cyclin E-labeling indexes between leiomyoma and leiomyosarcoma were statistically significant, no significant differences were found in the other markers. Furthermore, cyclin A- and/or E-positivity predicted a poor prognosis in recurrence- or metastasis-free survivals and overall survival. Immunoblotting revealed that cyclins A and E were expressed, in complex with cdk2, exclusively in tumors. In addition, not only leiomyosarcoma, but also leiomyoma specimens that exhibited negligible levels of complex expression, manifested detectable cdk2 activity. These results suggest 1) up-regulation of active cyclin A/cdk2 expression and associated kinase activity is critical for unrestrained cell proliferation; 2) cyclin E/cdk2 complexes may play a crucial role in leiomyosarcoma; 3) immunohistochemical detection of cyclins can be a more reliable tool for differential diagnosis between leiomyoma versus leiomyosarcoma than that of Ki-67 or proliferating cell nuclear antigen, and be a possible prognostic indicator.
Noguchi
T
T
Departments of Pathology and Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Dobashi
Y
Y
Minehara
H
H
Itoman
M
M
Kameya
T
T
D000328:Adult; D000368:Aged; D042846:CDC2-CDC28 Kinases; D002455:Cell Division / Q000502:physiology; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism / Q000502:physiology*; D000070819:Discoidin Domain Receptor 1; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D007889:Leiomyoma / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007890:Leiomyosarcoma / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
D016213:Cyclins; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; C092030:DDR1 protein, human; D000070819:Discoidin Domain Receptor 1; D020794:Receptor Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases