2005 Galloway Memorial Lecture: Breast phyllodes tumours--morphology and beyond.

OBJECTIVES The aims of this study were to evaluate the predictive role of morphology in a series of breast phyllodes tumours (PTs) in Asian women, and to determine the utility of immunohistochemical expression of p53 and CD117 in the stromal component. MATERIALS AND METHODS Breast PTs, diagnosed between January 1992 and December 2002 at the Department of Pathology, Singapore General Hospital, were classified into benign, borderline and malignant categories. Surgical margins were evaluated as complete or diffusely involved. Patient follow-up was obtained from casenotes and the Singapore Cancer Registry. Tissue microarrays (TMAs) were constructed using the 2-mm punch on the Beecher arrayer. p53 and CD117 immunohistochemistry was applied on 4-microm sections cut from TMA blocks. Immunostaining intensity was graded as 0, 1+, 2+ or 3+, for nil, weak, moderate and strong reactivity. The proportion of stromal cells decorated was assessed. Statistical analysis utilised the software SPSS for windows 11.5. Survival curves were plotted using the Kaplan-Meier method, while multivariate analysis was accomplished using the stepwise Cox proportional hazards model. A P value of <0.05 was considered a significant result. For verification of protein expression results, a pure stromal population derived from laser capture microdissection was subjected to real-time polymerase chain reaction to determine p53 and CD117 mRNA upregulation. RESULTS Three hundred thirty-five women diagnosed with PT were aged 16 to 69 years (median, 42 years). Tumour size ranged from 0.9 to 25 cm (median, 4 cm). Histologic classification revealed 250 (74.6%) benign, 54 (16.1%) borderline and 31 (9.3%) malignant PTs. Surgical margins were focally involved in 186 (55.5%) cases, diffusely affected in 9 (2.9%) cases and complete in 139 (41.5%) cases. Stromal cells positively stained ranged from 1% to 80% (mean, 15%; median, 5%) for p53, and 1% to 25% for CD117 (mean, 8%; median, 3%). p53 and CD117 staining was associated with PT grade (P = 0.004, P <0.001). Forty-three (12.8%) women suffered 57 recurrences (mean and median follow-up of 30.3 and 20.4 months respectively). Nine (2.7%) died during follow-up, 7 from malignant disease (mean and median survival duration 37.6 and 23.6 months respectively). Complete margins (P = 0.033) resulted in reduced recurrence risk by 51.7%. Though tumour grade was associated with an increased hazard of 1.63, it was not significant (P = 0.28). Immunoexpression of p53 was not associated with recurrence (P = 0.447), while CD117 was (P = 0.001). Upregulation of p53 and CD117 mRNA was found in cases in which there was protein overexpression. CONCLUSIONS Involved surgical margins remain a key prognostic parameter in breast PT. Death from disease occurred in women with malignant PTs at presentation, underscoring the need to manage this group more aggressively. p53 staining can be used to corroborate malignancy in PT. CD117 was predictive of recurrence, and if further validated, its expression can be explored for therapeutic purposes. Preliminary molecular studies verify mRNA upregulation in p53 and CD117 overexpressed cases.