1. ¹Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong
2. ²Department of Pathology, National University Hospital, Singapore
3. ³Department of Pathology, United Christian Hospital, Hong Kong
4. ⁴Department of Pathology, University of Sydney, Sydney, Australia
5. ⁵Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney, Australia
6. ⁶Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong

Correspondence: GMK Tse, FRCPC, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Ngan Shing Street, Shatin, NT, HKSAR, China. E-mail: garytse@cuhk.edu.hk

Received 2 November 2003; Revised 18 December 2003; Accepted 18 December 2003; Published online 26 March 2004.

Abstract

Mammary phyllodes tumors are uncommon stromal neoplasms, and are divided into benign, borderline and malignant groups basing on histologic criteria. While benign phyllodes tumors may recur, borderline phyllodes tumors show higher propensity to recur locally and rarely metastasize, and malignant phyllodes tumors show even higher chances of local recurrences or distant metastases. c-kit is a proto-oncogene that encodes a tyrosine kinase receptor (CD117) and is a marker for gastrointestinal stromal tumors (GIST). With the advent of therapeutic agent targeted at this receptor for GIST, we investigated 179 phyllodes tumors (101 benign, 50 borderline, 28 malignant) for c-kit expression using immunohistochemistry. The staining was compared to the degree of malignancy, and to the degree of stromal cellularity, mitotic activity, nuclear pleomorphism and stromal overgrowth. The overall positive rate for c-kit was 29% (52/179) and 17% (17/101), 24% (12/50) and 46% (13/28), respectively, for benign, borderline malignant and frank malignant phyllodes and the differences between all categories were significant (²=13.844, P=0.001). In mammary phyllodes tumors, there was increasing c-kit expression with increasing degree of malignancy, up to 46% in malignant cases. This provides strong evidence that c-kit receptor mediated tyrosine kinase involvement in the pathogenesis of phyllodes tumors, and the therapeutic agent, STI571, Glivec, may be a potentially useful drug for its management.