Expression of EphA2 and Ephrin A-1 in Carcinoma of the Urinary Bladder

Abraham, Shaji; Knapp, Deborah W.; Liu, Cheng; Snyder, Paul W.; Mittal, Suresh K.; Bangari, Dinesh S.; Kinch, Michael S.; Wu, Lun; Dhariwal, Jay; Mohammed, Sulma I.

doi:10.1158/1078-0432.ccr-05-1505

Cited by 98 publications

(86 citation statements)

References 33 publications

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“…EphA2 overexpression has been reported to correlate with aggressive features in other human tumor types [10][11][12][13][14][15][16][17][18][19]. Consistent with these reports, we found a significant increase in EphA2 expression in pancreatic cancers as compared to benign ducts and PanIN lesions, as well as increased expression in poorly differentiated carcinomas compared to well or moderate differentiated carcinomas (P < 0.005).…”

Section: Discussionsupporting

confidence: 90%

“…Instead, ephrinA binding seems to regulate EphA2 subcellular localization and interaction with other downstream signaling proteins including FAK and the MAP/ERK signaling pathways [8,9]. EphA2 is overexpressed in a variety of human cancers, and high levels of EphA2 are associated with aggressive disease and poor clinical outcomes [10][11][12][13][14][15][16][17][18][19]. In vitro studies have shown that EphA2 is a powerful oncoprotein, sufficient to confer malignant potential on non-transformed epithelial cells [7].…”

Section: Introductionmentioning

confidence: 99%

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Patterns of EphA2 protein expression in primary and metastatic pancreatic carcinoma and correlation with genetic status

Mudali

Lakkur

et al. 2006

Clin Exp Metastasis

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EphA2 is a transmembrane receptor tyrosine kinase that functions in the regulation of cell growth, survival, angiogenesis, and migration and EphA2 targeting has been proposed as a novel therapeutic strategy for neoplasms that overexpress this protein. EphA2 overexpression has been correlated with increased invasive and metastatic ability in pancreatic cancer cell lines. However, the patterns of EphA2 expression in human pancreatic cancers and associated metastases is unknown, as are the genetics of EphA2 in this tumor type. We collected clinicopathologic data and paraffin-embedded materials from 98 patients with primary and/or metastatic pancreatic cancer and performed immunohistochemical labeling for EphA2 protein. EphA2 protein immunolabeling was found in 207 of 219 samples (95%). The expression was predominantly cytoplasmic, although predominant membranous staining was observed in a minority of cases. When evaluated specifically for labeling intensity, primary and metastatic carcinomas were more strongly positive compared to benign ducts and PanIN lesions (P < 0.00001 and P < 0.01, respectively) and poorly differentiated carcinomas were more strongly positive for EphA2 than well and moderately differentiated tumors (P < 0.005). When primary carcinomas without metastatic disease were specifically compared to carcinomas with associated metastatic disease, the advanced carcinomas showed relatively less strong positive labeling for EphA2 (P < 0.008). Moreover, decreased EphA2 labeling was more commonly found in liver (P < 0.002), lung (P < 0.004) or peritoneal metastases (P < 0.01) as compared to distant lymph node metastases (P < 0.01). Genetic sequencing of the tyrosine kinase domain of EPHA2 in 22 samples of xenograft enriched pancreatic cancer did not reveal any inactivating mutations. However, EPHA2 amplification was found in 1 of 33 pancreatic cancers corresponding to a lymph node metastasis, indicating EPHA2 genomic amplification may underlie EphA2 overexpression in a minority of patients. Our data confirms that EphA2 is overexpressed in pancreatic cancer, but suggests a relative loss of EphA2 in co-existent pancreatic cancer metastases as well as a role for EPHA2 in organ specific metastasis.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Patterns of EphA2 protein expression in primary and metastatic pancreatic carcinoma and correlation with genetic status

Mudali

Lakkur

et al. 2006

Clin Exp Metastasis

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“…This pattern was also reported on EphB4 expression in breast carcinomas, 31 EphA2 expression in bladder carcinomas, 32 and EphA7 expression in hepatocellular carcinomas. 18 The post-transcription regulation mechanisms interpreted EphB4 and EphA2 differential expression between protein and transcript.…”

Section: Downregulation Of Epha1 In Colorectal Carcinomassupporting

confidence: 80%

Downregulation of EphA1 in colorectal carcinomas correlates with invasion and metastasis

et al. 2009

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The Eph gene family has important roles in the developmental processes and may also be involved in the initiation, progression, and metastasis of certain types of cancers. In the present study, quantitative real-time reverse-transcriptase PCR was performed to detect the expression of EphA1 transcript in 5 colon cancer cell lines and 75 colorectal carcinomas. Immunohistochemical staining was used to check the expression of EphA1 protein in 20 colorectal adenomas and in 111 colorectal carcinomas specimens. EphA1 protein expression was not completely consistent with transcript expression. EphA1 protein was expressed in all adenomas and reduced in 54% colorectal cancers. Reduced expression of EphA1 protein occurred more often in male patients (P ¼ 0.028) and in patients with poor differentiation (P ¼ 0.027), greater depth of wall invasion (P ¼ 0.003), lymph node metastasis (P ¼ 0.034), and advanced tumor stage (P ¼ 0.003). Patients with reduced EphA1 expression had a poor overall survival (P ¼ 0.059). Reduced EphA1 expression in patients over 55 years or with rectal cancers and sigmoid colon cancers is associated with a poor overall survival (P ¼ 0.034 and 0.015, respectively). Our data indicate that the EphA1 may play different roles during the different stages of colorectal carcinoma progression.

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“…EFNA1 expression has been observed in tumor cells and in endothelial cells and has been shown to induce endothelial cell migration (18), capillary assembly in vitro and corneal angiogenesis in vivo (19). EFNA1 and EPHA2 expression is associated with carcinogenesis, angiogenesis (18,(20)(21)(22), and tumorigenesis in various types of cancer (23)(24)(25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

Association between ephrin-A1 mRNA expression and poor prognosis after hepatectomy to treat hepatocellular carcinoma

Wada

Yamamoto

Kim

et al. 2014

International Journal of Oncology

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Abstract. Hypoxia regulates the expression of genes that promote tumor growth, angiogenesis and invasion. We previously studied hypoxic tumor cells in vitro and from hepatic metastases of colorectal cancer and determined several potential prognostic factors for hepatocellular carcinoma (HCC). In this study, we evaluated the prognostic impact of the expression of ephrin-A1 (EFNA1) and its receptor, EPHA2, in patients with HCC after curative resection. Samples from a total of 139 HCC patients were analyzed by either microarray alone (n=86) or by microarray and quantitative PCR (n=53). There was no correlation between EFNA1 expression and clinicopathological factors. EPHA2 expression was not significantly correlated with any clinicopathological factors, except for microscopic portal invasion. EFNA1 was an independent prognostic factor for HCC (p=0.0277). These findings suggest that EFNA1 expression may be a useful marker for predicting high risk of recurrence in patients who have undergone curative resection for HCC.

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Expression of EphA2 and Ephrin A-1 in Carcinoma of the Urinary Bladder

Cited by 98 publications

References 33 publications

Patterns of EphA2 protein expression in primary and metastatic pancreatic carcinoma and correlation with genetic status

Patterns of EphA2 protein expression in primary and metastatic pancreatic carcinoma and correlation with genetic status

Downregulation of EphA1 in colorectal carcinomas correlates with invasion and metastasis

Association between ephrin-A1 mRNA expression and poor prognosis after hepatectomy to treat hepatocellular carcinoma

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