CD117 expression in breast phyllodes tumors correlates with adverse pathologic parameters and reduced survival

Abstract

and 5 Duke-NUS Graduate Medical School, Singapore 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 (Po0.001), increased stromal hypercellularity (P ¼ 0.003), stromal atypia (P ¼ 0.01), and stromal mitotic activity (Po0.001), permeative microscopic margins (P ¼ 0.002), and presence of hemorrhage (P ¼ 0.001). Expression was also associated with poorer overall survival (P ¼ 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.

Mutational analysis of MED12 exon 2 in a spectrum of fibroepithelial tumours of the breast: implications for pathogenesis and histogenesis

“…Although mostly a localized lesion, a small portion of PTs, particularly malignant PTs, behave aggressively and can metastasize similarly to a sarcoma . Although the overexpression of several markers in PTs has suggested the potential aetiological roles of pathway dysregulation involving these markers, conclusive evidence regarding the pathogenesis of PTs is limited . Fibroadenomas (FAs) and PTs are the two main prototypes of fibroepithelial tumours.…”

Associations of epithelial c-kit expression in phyllodes tumours of the breast

“…Thus epithelial c-kit may affect the role of stromal c-kit in the development and malignant progression of PT. Previous analysis has shown the role of stromal c-kit in PT prognostication 9 11. Given the influences of epithelial c-kit expression on the relationship between stromal c-kit and malignant PT features, it will be interesting to validate the results with an independent cohort and to test whether epithelial c-kit expression might affect the prognostic power of stromal c-kit.…”

“…Some smaller series showed an absence or weak correlation of stromal c-kit with PT grading,6 7 whereas other series demonstrated association of increased stromal c-kit expression with increasing degree of malignancy 8–13. Also, c-kit stromal staining was reported to be predictive for recurrence 9 11. As PT are biphasic, both epithelial and stromal components are believed to be integral to their pathogenesis.…”

Large Malignant Phyllodes Tumor of the Breast with Metastases to the Lungs

“… 17-19 Most recently, expression of CD117 (KIT) was shown to be associated with unfavorable pathologic criteria and worse prognosis in patients with PT, although no mutations in the CD117 gene were identified. 20 A novel development in PT research is the identification of microRNA-21 as an independent prognostic predictor of recurrence and metastasis, and miR-21’s role as an accelerator of PT growth and metastasis is currently being explored. 21 …”