Breast carcinoma with a high histologic grade is highly invasive and metastatic. One reason for its irregular morphology is the formation of excessive protrusions due to assemblages of branched actin filament networks. In mammalian cells, the
actin-related protein 2 and 3 (
Arp2/3) complex initiates actin assembly to form lamellipodial protrusions by binding to the
Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein2 (WAVE2), a member of the
WASP protein family. In this study, the localization Arp2 and WAVE2 in
breast carcinoma was investigated to clarify whether coexpression of the two
proteins is associated with histologic grade or patient outcome. Immunohistochemical staining of Arp2 and WAVE2 was performed on mirror specimens of 197
breast carcinomas, and the association between coexpression of the two
proteins and clinicopathologic factors was examined. Kaplan-Meier disease-free survival and overall survival curves were analyzed to determine the prognostic significance of Arp2 and WAVE2 coexpression in
breast carcinoma. Coexpression of Arp2 and WAVE2 was detected in 64 (36%) of 179 invasive
ductal carcinomas and in 2 (11%) of 18
ductal carcinomas in situ, but was not detected in any adjacent non-cancerous tissue. The proportion of
cancer cells expressing both Arp2 and WAVE2 was significantly higher in cases with high histologic grade (P<0.0001), and cases with
lymph node metastasis (P=0.0150). The patients whose
cancer cells showed such coexpression had shorter disease-free (P=0.0002) and overall survival (P=0.0122) than patients whose
cancer cells expressed only one or none of Arp2 and WAVE2. Multivariate Cox regression analysis revealed that coexpression of Arp2 and WAVE2 is an independent factor for both
tumor recurrence (P=0.0308) and death (P=0.0455). These results indicate that coexpression of Arp2 and WAVE2 is a significant prognostic factor that is closely associated with aggressive morphology of invasive
ductal carcinoma of the breast.