الفهرس 
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Abstract
Osteosarcoma is the most common primary bone malignancy and accounts for approximately 47.75 % of primary bone malignant tumors according to Egyptian National Cancer Institute data.
Ezrin, also known as cytovillin or villin2, is a member of ERM (Ezrin-Radixin-Moesin) family, which acts as a member organizer and linkers between plasma membrane and cytoskeleton. The erbB family tyrosine kinases play an important role in the control of cell cycle, proliferation and migration of normal and cancer cells. Expression of erbB members is linked to poor prognosis in numerous epithelial and mesenchymal malignant tumors.
The aim of this study was to assess the immunohistochemical expression of ezrin and HER2/neu in osteosarcoma and to correlate their expression with the available clinicopatholgical parameters. This study was carried out on 67 bone cases including 57 cases of osteosarcoma and 10 normal bone specimens retrieved from the archive of Pathology Department, National Cancer Institute, Cairo University and Pathology Department Faculty of Medicine, Menofyia University, during the period between March 2000 and June 2012.
Of the collected 57-osteosarcoma cases, 38 were males (66.7 %) and 19 were females (33.3%) with a male to female ratio of 2:1. Their ages ranged fom 4 to 75 years with a mean ± SD of 21.98 ± 12.88 years.
Most of the selected cases (89.5%) were located in the extremities while the remaining cases (10.5%) were of axial location. Tumors measured equal or less than 8cm in maximal diameter constituted 57.9% of our cases. Twenty cases (41.9%) had distant metastasis while only nine cases (15.8%) had local recurrence. Nineteen cases (33.3%) died of their disease in a period ranged between 2 to 54 months.
Histopathological examination of osteosarcoma cases revealed that 27 (47.4%) were osteoblastic, 17 (29.8%) were chondroblastic, 3 (5.2%) were fibroblastic, 9 (15.7%) were fibrohistocytic (MFH-like variants) and 1 (1.8%) was small cell type. Most of the cases (37/57, 64.9%) were of high-grade category and thirty-two cases (56.1%) were of advanced stage.
In this study, osteosarcoma patients exhibited either metastasis/ recurrence or both showed significant association with stage grouping (P=0.001), and with survival time (P=0.001).
Immunoreactivity for ezrin revealed pure cytoplasmic staining in the studied osteosarcoma cases. All the ten normal bony specimens showed negative ezrin expression, while 47 (82.5%) of the studied osteosarcoma cases showed positive ezrin expression with a highly statistically significant differences between them (P=0.0001), and 25 (53.2%) of the positive osteosarcoma cases showed high ezrin expression.
Positive ezrin expression was significantly associated with young age (< 25 years) (P=0.01), high grade (P=0.001) and short survival time (P=0.0001). Furthermore, high ezrin expression was significantly associated with high-grade cases (P=0.001).
HER2/neu immunoreactivity showed cytoplasmic and or membranous staining in the studied osteosarcoma cases. The entire normal bony specimen showed negative HER2/neu expression, while 41 (71.9%) out of the 57-osteosarcoma cases showed HER2/neu positivity with highly statistically significant differences between them (P=0.0001). Pure cytoplasmic staining was noticed in 78% (32/41) of the positive cases and membranous pattern of expression was observed in the remaining 22% (9 /41).
Positive HER2/neu expression was significantly associated with osteosarcoma cases presented with high-grade tumor (P=0.04). There was no significant impact of the pattern of HER2/neu expression either cytoplasmic or membranous on the studied clinico-pathological parameters. However, 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, since 92.6% of HER2/neu positive cases were also positive for ezrin (P=0.02).
By applying Lo Rank equation we found a significant poor impact of stage grouping (P=0.0001), metastasis (P=0.0001), and recurrence (P=0.01) on the overall survival of osteosarcoma patients. By multivariate analysis, metastasis (P=0.02) and recurrence (P=0.05) were the independent prognostic factors affecting patient`s survival.