Stromal Matrix Metalloproteinase-14 Expression Correlates With the Grade and Biological Behavior of Mammary Phyllodes Tumors

Abstract

Phyllodes tumors (PTs) of the breast are rare biphasic tumors with the potential for invasion and metastatic spread. Matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) are involved in several key aspects of tumoral growth, invasion, and metastasis, but little is known of their expression in PTs. The objective of this study was to assess the expression of MMPs and TIMPs in PTs and to determine their association with grade and clinical behavior of PTs. Eighty-two PTs (50 benign, 22 borderline, and 10 malignant) were studied. Automated immunohistochemical staining for MMP-1, -2, -7, -9, -11, -13, and -14 and TIMP-1, -2, and -3 was performed using tissue microarray blocks and the expression of MMPs and TIMPs was assessed in the stromal component. There were no significant differences in the expression of stromal MMPs and TIMPs in the 3 groups of PTs, except for MMP-14. There was a significant increase in stromal MMP-14 expression with increasing PT grade (P<0.01). The stromal MMP-14 expression in the borderline and malignant PTs was higher than that in benign PTs (P<0.05 and P<0.05, respectively). Furthermore, the expression of stromal MMP-14 was associated with a higher rate of recurrence (P<0.05). Our results show for the first time that stromal MMP-14 expression is associated with the grade and clinical behavior of PTs of the breast.