title: CD117 expression in breast phyllodes tumors correlates with adverse pathologic parameters and reduced survival.
abstract: CD117 (c-kit) is a type III receptor tyrosine kinase encoded by the KIT gene. Deregulation of expression and mutations in the gene are implicated in various tumors. Reports of CD117 expression in phyllodes tumors have been controversial. We aim to investigate the protein expression of CD117 and mutations in the KIT gene in phyllodes tumors, and correlate the findings with pathological parameters and clinical outcome. A total of 272 cases were included in this study. CD117 expression was investigated by immunohistochemistry on tissue microarray sections. Toluidine blue staining was performed to indicate mast cells. Overall, 28 (10%) cases were CD117 positive. CD117 expression was significantly associated with tumor grade (P<0.001), increased stromal hypercellularity (P=0.003), stromal atypia (P=0.01), and stromal mitotic activity (P<0.001), permeative microscopic margins (P=0.002), and presence of hemorrhage (P=0.001). Expression was also associated with poorer overall survival (P=0.003). Nineteen cases were further selected for mutation screening through the Affymetrix OncoScan platform. No mutation of the KIT gene was found. Despite a lack of mutations in the KIT gene, CD117 protein expression is associated with unfavorable pathological parameters and poorer prognosis, suggesting an underlying role in the biology of phyllodes tumors.
authors.affiliation: 1] Department of Pathology, Singapore General Hospital, Singapore [2] Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Wai Jin
authors.initials: WJ
authors.lastname: Tan
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Aye Aye
authors.initials: AA
authors.lastname: Thike
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Sie Yong
authors.initials: SY
authors.lastname: Tan
authors.affiliation: Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong.
authors.forename: Gary M-K
authors.initials: GM
authors.lastname: Tse
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore.
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Tan
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Boon Huat
authors.initials: BH
authors.lastname: Bay
authors.affiliation: 1] Department of Pathology, Singapore General Hospital, Singapore [2] Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore [3] Duke-NUS Graduate Medical School, Singapore.
authors.forename: Puay Hoon
authors.initials: PH
authors.lastname: Tan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D003557:Phyllodes Tumor / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis* / Q000235:genetics; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019009:Proto-Oncogene Proteins c-kit