The Prognostic Role of Ezrin and HER2/neu Expression in Osteosarcoma

Abstract

Osteosarcoma is the most common primary malignant bone tumor in Egypt. Ezrin is involved in cell adhesion to the extracellular matrix and in cell-cell interactions facilitating metastasis. HER2/neu is overexpressed in breast cancer and other types of cancer. This study aimed to assess the expression of ezrin and HER2/neu in 57 primary osteosarcoma cases and to correlate their expression with the available clinicopathologic parameters and the overall, metastasis-free and event-free survival. Both ezrin and HER2/neu were not expressed in the normal bone and they were upregulated in 82.5% and 71.9% of osteosarcoma, respectively. Positive ezrin expression was significantly associated with young age (below 25 y) (P=0.01), high grade (P=0.001), and short survival time (P=0.0001). Positive HER2/neu expression was significantly associated with high-grade osteosarcoma (P=0.04). Membranous HER2/neu expression was the only factor that showed significant impact on metastasis-free (P=0.002) and event-free survival (P=0.002). Ezrin was significantly correlated with HER2/neu expression (P=0.02). Advanced stage (P=0.0001), metastasis (P=0.0001), and recurrence (P=0.01) were the factors affecting the overall survival of osteosarcoma patients. Ezrin and HER2/neu are overexpressed and coexpressed in osteosarcoma with adverse prognostic features such as high grade. Membranous pattern of HER2/neu seems to be more important than the cytoplasmic pattern because of its impact on metastasis-free and event-free survival. Therefore, ezrin and HER2/neu could be potential prognostic markers and treatment targets for osteosarcoma.

The clinical prognostic significance of ezrin in patients with bone and soft tissue sarcomas: a meta‐analysis

“…Several limitations of the present meta-analysis should be considered. First, although the results showed there was no obvious publication bias, some other potential sources of publication bias should be taken into consideration, such as unpublished negative results [22] or studies that could not be included due to language limitations. Second, most of the HRs and the corresponding 95% CIs were extracted indirectly, and there was obvious uniformity in terms of the definitions of survival outcomes, which might have an impact on the reliability of our results.…”

“…For further eligibility evaluation, the full-text articles were read, and five studies were removed because of overlapping data (n = 2) and insufficient data (n = 3). Therefore, 19 studies [17,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] with 1316 bone and soft tissue sarcoma patients were included in the meta-analysis, and data from 13 studies were used to evaluate the clinicopathological significance and data from 17 studies were used to evaluate the prognostic value of ezrin expression. A flow diagram of the selection process is shown in Fig.…”

The clinical significance of changes in ezrin expression in osteosarcoma of children and young adults

“…Our study was limited to the analysis of high-grade osteosarcomas. Abdou et al [39] assessed the expression of ezrin and HER2/neu in 57 primary osteosarcomas in association with clinicopathological parameters and survival. Positive ezrin expression was significantly correlated with high grade, short survival time, and age below 25 years.…”

Chimeric antigen receptor T (CAR-T) cell immunotherapy for sarcomas: From mechanisms to potential clinical applications

“…HER2 expression correlates with clinical features in various sarcomas including osteosarcoma, synovial sarcoma, and Ewing's sarcoma [21][22][23][24][25][26]. In one such example, expression of HER2 correlates with worse histologic response and survival for osteosarcoma patients [27,28]. Although the anti-HER2 antibody (trastuzumab) was found to be ineffective in osteosarcoma treatment [29], there are opportunities within the realm of immunotherapy.…”