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Entity | Various cancers |
Note | EphA2 has been reported to be overexpressed in several cancers and a high level of EphA2 has been detected in malignant cancer-derived cell lines and advanced forms of cancer. |
Prognosis | Eph-A2 overexpression was significantly associated with poor prognosis in several types of malignant tumors, including oral tongue, oesophageal, lung, renal, ovarian, cervical and endometrial carcinoma, as well as glioblastoma and melanoma. In human epidermal growth factor receptor 2 (Her2) positive breast cancer patients, increased levels of EphA2 mRNA were correlated to a decreased potential for overall and disease-free survival. |
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Entity | Epithelial ovarian carcinoma |
Note | High EphA2 expression was evident in clinical specimens of invasive ovarian tumors, while little or no staining was observed in normal ovaries. Moreover, EphA2 overexpression was significantly associated with higher grade, advanced disease stage and with factors involved in invasion and angiogenesis. A relationship between EphA2 overexpression and the status of tumor suppressor p53 was noted. High EphA2 expressing tumors exhibited increased microvessel density when stained for CD31 as a measure of angiogenesis. In addition, the matrix metalloproteinase expression, which degrades the extracellular matrix during cancer progression, was also associated with EphA2 expression. |
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Entity | Prostate cancer |
Note | In clinical prostate carcinoma specimens, EphA2 immunoreactivity was increased with a positive staining in 60-100% of cells. EphA2 was overexpressed more in metastatic cells compared to non-invasive prostatic epithelial cells and its levels as increased as prostatic epithelial cells moved toward a more aggressive phenotype. |
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Entity | Breast cancer |
Note | In breast carcinoma specimens, 92% of the cases showed moderate to high staining for EphA2. EphA2 overexpression in breast cancer was negatively associated with estrogen receptor expression. In clinical specimens of benign mammary epithelia, 75% of the specimens were negative, while 25% were weak positive. |
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Entity | Pancreatic carcinoma |
Note | EphA2 was overexpressed in about 95% of pancreatic cancer specimens, being associated with metastatic disease, increased cellular invasiveness and patients' age. |
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Entity | Lung cancers |
Note | In non-small cell lung cancer specimens, moderate to high EphA2 immunostaining was observed in the membrane and cytoplasm in more than 70% of the examined carcinomas. This increase was comparable in adenocarcinoma, squamous cell carcinoma and large cell carcinomas. EphA2 was also associated with clinically advanced stages of disease, the presence of brain metastasis and smoking status. |
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Entity | Brain cancers |
Note | EphA2 was found to be overexpressed but not to be tyrosine phosphorylated in glioblastoma multiforme cells or tumors. In surgically resected human malignant glioma tissues, a heterogeneous and variable EphA2 staining pattern was observed. Although normal brain tissues exhibited minimal EphA2 staining, the cases of anaplastic astrocytoma and glioblastoma multiforme exhibited variable staining patterns. In astrocytic tumors, EphA2 overexpression was also correlated with the pathological grade and the proliferation status of tumors. |
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Entity | Urinary bladder carcinoma |
Note | Clinical specimens of urinary bladder carcinoma when examined by a semi-quantitative immunostaining showed a differential staining pattern than normal specimens. Of all urinary bladder specimens with Ta grade lesions, 30% showed moderately strong staining, while in the T3 and T4 lesions, 75% and 90% of the samples showed strong staining, respectively. In sharp contrast, 85% of normal tissues showed weak staining, while the remaining 15% showed moderate staining for EphA2. Notably, EphA2 staining intensity was associated with advanced stage of urothelial carcinoma. |
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Entity | Melanoma |
Note | EphA2 was found to be phosphorylated in aggressive melanoma-derived cells and was associated with vasculogenic mimicry, i.e. the formation of endothelial cell-like network. In a tissue microarray of melanomas, strong cytoplasmic EphA2 staining was present in 16% of the cases, being associated with histological thickness of melanomas and tumors proliferation status. A correlation of metastatic potential and high EphA2 expression was also observed in human melanoma cell lines derived from patients, while EphA2 overexpression changed cellular migration from the mesenchymal- to the amoeboid-type. |
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Entity | Oesophageal squamous cell carcinoma |
Note | EphA2 overexpression was detected in esophageal carcinoma-derived cells and in 50% of clinical specimens. EphA2 expression was correlated with lymph node metastases, whereas no significant association with patients' age, tumour location, tumour size, histological differentiation and clinical stage was noted. |
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Entity | Colorectal carcinoma |
Note | Increased expression of EphA2 was observed in over 59% of clinical specimens from colorectal cancer patients. EphA2 expression was increased in early-stage tumors compared to those of advanced stage, as well as in smaller tumors than large tumors. Microvessel count was also correlated with overexpression of EphA2. In human colon cancer-derived HCT116 cells, a dose and time-dependent upregulation of EphA2 was noticed after treatment with deoxycholic acid, a component of bile acids and promoter of colon cancer. The upregulation of EphA2 was p53-independent, but it was linked to the activation of MAP kinase pathway. |
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Entity | Renal cell carcinoma |
Note | Higher levels of EphA2 expression were correlated with tumors that were of higher grade, larger and more highly vascularized in patients with renal cell carcinoma. |
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Entity | Vulvar carcinoma |
Note | In vulvar cancers, more than 50% of vulvar squamous cell carcinomas expressed elevated levels of EphA2. |
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Entity | Malignant and benign thyroid malignancies |
Note | Eph-A2 receptor was associated with increased proliferative activity of malignant thyroid lesions. Eph-A2 was significantly overexpressed in malignant compared to benign thyroid lesions. Papillary carcinoma cases also presented significantly increased Eph-A2 expression compared to those with hyperplasia nodules. |
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Entity | Squamous cell cervical carcinomas |
Note | In early squamous cell cervical carcinomas, EphA2 expression was classified as negative in 21 tumors (10%), weak positive in 108 tumors (50%), moderate positive in 69 (32%) and strong positive in 19 tumors (9%). |
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Entity | Oral tongue squamous cell carcinoma |
Note | In oral tongue SCC specimens, Eph-A2 expression was significantly correlated with tumor size, clinical stage, lymph invasion, recurrence and distant metastasis. |
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PMID 22236865 |
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PMID 12576426 |
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PMID 16300469 |
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PMID 12494475 |
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Patterns of EphA2 protein expression in primary and metastatic pancreatic carcinoma and correlation with genetic status. |
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The EPHA2 gene is associated with cataracts linked to chromosome 1p. |
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PMID 19144211 |
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Increased expression of EphA2 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients. |
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Mutations of the EPHA2 receptor tyrosine kinase gene cause autosomal dominant congenital cataract. |
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