Original Article

Modern Pathology (2008) 21, 1238–1245; doi:10.1038/modpathol.2008.78; published online 23 May 2008

Expression of c-kit in fibroepithelial lesions of the breast is a mast cell phenomenon

Bojana Djordjevic1 and Wedad M Hanna1

1Department of Pathology, Sunnybrook and Women's College Health Sciences Centre, University of Toronto, Toronto, ON, Canada

Correspondence: Dr W Hanna, MD, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room E4 32, Toronto, ON M4N 3M5, Canada. E-mail: wedad.hanna@sunnybrook.ca

Received 11 December 2007; Revised 21 March 2008; Accepted 24 March 2008; Published online 23 May 2008.

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Abstract

The expression of c-kit, a protooncogene tyrosine kinase receptor (CD117), in phyllodes tumors of the breast has been the subject of recent investigations. We examined stromal c-kit expression by immunohistochemistry in 68 cases comprising fibroadenomas, fibroadenomas with cellular stroma, and benign, borderline, and malignant phyllodes tumors. Membrane staining was identified in the epithelium of 82% of cases, representing all diagnostic categories in the study. Membrane and cytoplasmic staining was detected in scant cells in the stroma in 74% of the cases in the study, again, across all diagnostic entities. However, when toluidine blue and tryptase staining was performed, the staining pattern matched that of c-kit in the number of cells and their distribution, thereby confirming the presence of mast cells and excluding any appreciable level of true stromal c-kit staining. One borderline and one malignant phyllodes tumor showed a diffuse weak stromal signal, which could not be accounted for by toluidine blue and tryptase. These cases were further tested for the presence of known activating mutations of c-kit and PDGFR-alpha, and yielded negative results. Our findings indicate that c-kit is an unlikely player in the pathogenesis of fibroepithelial lesions of the breast. The positive stromal staining suggested previously by other authors may be attributed to mast cells. C-kit, therefore, has neither a diagnostic nor a prognostic role in phyllodes tumors, and there is no rationale for the treatment of recurrent of malignant phyllodes tumor patients with tyrosine kinase inhibitors.

Keywords:

c-kit, CD117, fibroepithelial lesion, phyllodes, fibroadenoma, mast cell

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