title: CDK8 Expression in Extrauterine Leiomyosarcoma Correlates With Tumor Stage and Progression.
abstract: Mediator is a multiprotein complex that acts as a versatile transcription coactivator in eukaryotes. CDK8 kinase complex is a 4-protein subunit of the mediator complex that can act as a transcriptional repressor or coactivator, depending on the specific pathways involved. Although the role of MED12 exon 2 mutations is documented in the pathogenesis of uterine leiomyomas, its role in extrauterine smooth muscle tumorigenesis is less clear. Similarly, there is a paucity of data on the role of CDK8 in extrauterine smooth muscle tumorigenesis and progression. Our study correlates immunohistochemical expression of CDK8 and MED12 with clinical and pathologic parameters in extrauterine leiomyosarcomas. Immunohistochemical expression of CDK8 and MED12 in leiomyosarcomas was correlated with the tumor grade, stage, and the presence of local recurrence or metastasis. MED12 was expressed in the majority of leiomyosarcomas regardless of their stage or grade. CDK8 expression was lost in 1 of 6 pT1 tumors, compared with 9 of 10 pT2 tumors (P=0.0076). When the second group was expanded to include those tumors that did not have a recorded pathologic stage but had local recurrence and distant metastases, the difference in CDK8 expression was also statistically significant. Loss of CDK8 expression by immunohistochemistry is more prevalent in somatic leiomyosarcomas presenting at a higher histopathologic stage, as well as with local and distant recurrence, and can be used to enhance the current predictive parameters.
authors.affiliation: Departments of Pathology.
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Yergiyev
authors.affiliation: Departments of Pathology.
authors.forename: George
authors.initials: G
authors.lastname: Garib
authors.affiliation: Departments of Pathology.
authors.forename: Karen
authors.initials: K
authors.lastname: Schoedel
authors.affiliation: Departments of Pathology.
authors.forename: Alka
authors.initials: A
authors.lastname: Palekar
authors.affiliation: Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: David
authors.initials: D
authors.lastname: Bartlett
authors.affiliation: Departments of Pathology.
authors.forename: Uma N M
authors.initials: UNM
authors.lastname: Rao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D056850:Cyclin-Dependent Kinase 8 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000503:physiopathology; D007890:Leiomyosarcoma / Q000503:physiopathology*; D008297:Male; D056892:Mediator Complex / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging
chemical_list: D014408:Biomarkers, Tumor; C460107:MED12 protein, human; D056892:Mediator Complex; C095686:CDK8 protein, human; D056850:Cyclin-Dependent Kinase 8