Ezrin in primary cutaneous melanoma

Abstract

Ezrin is a member of the ezrin-radixin-moesin family of proteins that link the actin-containing cytoskeleton to the plasma membrane. Ezrin is also connected to signaling molecules involved in the regulation of cell survival, proliferation and migration. Here, we examined the expression of ezrin in 95 primary cutaneous melanomas and correlated ezrin expression with conventional prognostic factors and biomarkers. From 12 patients metastatic tissue samples were also examined. In addition to ezrin staining, Mib-1 proliferation antigen, p53 and Bcl-2 were evaluated. Ezrin immunoreactivity was seen in most tumors; only 19 (20%) melanomas were negative. A total of 48 (51%) tumors had weak immunoreactivity and 28 (29%) strong immunoreactivity. The intensity of ezrin immunoreactivity was associated with tumor thickness (Breslow, P ¼ 0.0008) and with tumor invasion level (Clark, P ¼ 0.004), thicker tumors having stronger immunoreactivity. Also, there was a correlation between higher Mib-1 index in tumors and strong ezrin expression. All metastatic samples (n ¼ 12) showed positive ezrin immunoreactivity. In univariate analysis of survival, patients (n ¼ 76) with positive ezrin immunoreactivity had worse clinical disease behavior than those (n ¼ 19) without ezrin immunoreactivity, but the difference was not significant (P ¼ 0.19). In multivariate analysis of survival, the ezrin immunoreactivity was not a significant marker. The results indicate that ezrin is expressed in most primary melanomas of the skin and in all metastatic tumors. Ezrin expression correlates with tumor thickness and level of invasion suggesting an association between ezrin expression and tumor progression.

Pleiotropic function of ezrin in human metastatic melanomas

“…52,53 Here, we have shown that transfection of metastatic melanoma cells with Nterminal 146 aminoacids of ezrin, fused to GFP (ez-146) abrogated metastatic potential in vivo.…”

The actin-cytoskeleton linker protein ezrin is regulated during osteosarcoma metastasis by PKC

“…Following suppression of ezrin in murine osteosarcoma cells, there were no changes in in vitro viability, proliferation or primary tumor growth in vivo . Despite expression of other ERM proteins, the suppression of ezrin in several murine and human cancer models resulted in the inhibition of metastasis (Makitie et al, 2001;Khanna et al, 2004;Pang et al, 2004;Yu et al, 2004;Ilmonen et al, 2005;Weng et al, 2005). This suggested that ezrin, rather than other ERM proteins, contributed a unique and necessary function to cells undergoing metastasis.…”

“…We have shown that ezrin is required for metastasis in two pediatric solid tumors of mesenchymal origin, osteosarcoma and rhabdomyosarcoma Yu et al, 2004). The expression of ezrin has been linked to poor survival in several cancers including carcinomas of the breast, colon, endometrium and ovary, cutaneous and uveal melanomas, brain tumors and soft tissue sarcomas (Ohtani et al, 1999;Khanna et al, 2004;Yu et al, 2004;Elliott et al, 2005;Ilmonen et al, 2005;Weng et al, 2005;Kobel et al, 2006;Bruce et al, 2007).…”

Ezrin expression is related to poor prognosis in FIGO stage I endometrioid carcinomas

“…3 Recent studies suggest a metastasis-promoting role for ezrin in several tumor entities by facilitating tumor cell motility. These include pancreatic carcinoma, 4 breast carcinoma, 5 ovarian carcinoma, 6,7 melanoma, 8 and osteosarcoma. 9 Furthermore, inhibition of ezrin by antisense oligonucleotides blocked invasiveness of endometrial adenocarcinoma cell lines.…”