Immunohistochemical expression of epidermal growth factor receptors in human adrenocortical carcinoma

Kamio, Takihiro; Shigematsu, Kazuto; Sou, Houhei; Kawai, Kioko; Tsuchiyama, Hideo

doi:10.1016/0046-8177(90)90227-v

Cited by 91 publications

(82 citation statements)

References 28 publications

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“…Nuclear expression of EGFR was further detected in other cell types and tissues, such as placentas, thyroids and immortalized epithelial cells of ovary and kidney origins (Cao et al, 1995;Lin et al, 2001;Marti et al, 2001;Lo et al, 2005a). High levels of EGFR was also found in the nuclei of many tumours, including those of skin, breast, bladder, cervix, adrenocorticord, thyroid and oral cavity (Kamio et al, 1990;Lipponen and Eskelinen, 1994;Lin et al, 2001;Marti et al, 2001;Lo et al, 2005a, c;Psyrri et al, 2005). In addition, EGFR has been shown to localize in the inner nuclear membrane (Cao et al, 1995;Klein et al, 2004).…”

Section: Detection Of Nuclear Egfrmentioning

confidence: 96%

“…Nuclear detection of EGFR was first reported in hepatocytes that underwent regeneration and in primary adrenocortical carcinomas more than a decade ago (Kamio et al, 1990;Marti et al, 1991). Nuclear expression of EGFR was further detected in other cell types and tissues, such as placentas, thyroids and immortalized epithelial cells of ovary and kidney origins (Cao et al, 1995;Lin et al, 2001;Marti et al, 2001;Lo et al, 2005a).…”

Section: Detection Of Nuclear Egfrmentioning

confidence: 98%

“…Known targets of nuclear FGFR include FGF-2, neurofilament-L and tyrosine hydroxylase (Peng et al, 2001(Peng et al, , 2002Stachowiak et al, 2003). In support of this notion, EGF, EGFR, TrkA/NGF receptor and the ligand NGF have been shown to bind to chromatins (Rakowicz-Szulczynska et al, 1988;Kamio et al, 1990) and Schwannoma-derived growth factor, a ligand for EGFR, bound to A þ T-rich DNA sequences (Kimura, 1993). Together, these data suggest an emerging role that nuclear receptors play in transcriptional regulation.…”

Section: Nuclear Egfr and Her-2 As Transcriptional Regulatormentioning

confidence: 99%

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Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival

2006

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Emerging evidences suggest the existence of a new mode of epidermal growth factor receptor (EGFR) signalling pathway in which activated EGFR undergoes nuclear translocalization and subsequently regulates gene expression and potentially mediates other cellular processes. This signalling route is distinct from the better-characterized, traditional EGFR pathway that involves transduction of mitogenic signals through activation of multiple signalling cascades. Transcriptional activity of nuclear EGFR appears to depend on its C-terminal transactivation domain and its physical and functional interaction with other transcription factors that contain DNAbinding activity. Likely via its ability to upregulate gene expression, nuclear EGFR pathway is associated with major characteristics of more aggressive tumours: increased proliferative potential, nitric oxide synthesis, and accelerated G1/S cell cycle progression. A role of nuclear EGFR in prognostic prediction is further suggested in patients with breast carcinomas and oropharyngeal squamous cell carcinomas. It is noted that significant advances were made towards the knowledge of the nuclear EGFR pathway; however, many aspects of this new pathway remain unresolved and will be discussed in this review. As a number of other receptor tyrosine kinases (RTKs) and cytokine receptors also undergo similar nuclear translocalization, a better understanding of the physiological and malignant nature of the nuclear EGFR pathway will likely shed light into the biology of cancer with nuclear RTKs.

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Section: Detection Of Nuclear Egfrmentioning

confidence: 96%

Section: Detection Of Nuclear Egfrmentioning

confidence: 98%

Section: Nuclear Egfr and Her-2 As Transcriptional Regulatormentioning

confidence: 99%

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Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival

2006

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“…Taken together, the results of these series show that EGFR was expressed in a vast majority of adrenocortical carcinoma samples (n ¼ 127). [31][32][33][34] However, none of these studies correlated EGFR expression with clinical outcome, nor did these studies analyze EGFR gene mutations. Therefore, we aimed at a comprehensive investigation of the EGFR system in adrenocortical carcinoma.…”

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confidence: 99%

Epidermal growth factor receptor in adrenocortical tumors: analysis of gene sequence, protein expression and correlation with clinical outcome

et al. 2010

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Adrenocortical carcinoma is a rare but highly malignant neoplasm with still limited treatment options. Epidermal growth factor receptor (EGFR) has been shown to be overexpressed in many solid tumors, but its expression in adrenocortical carcinoma has been studied only in a limited number of cases. Therefore, we analyzed the expression of EGFR in 169 adrenocortical carcinoma samples and compared it with 31 adrenocortical adenomas. Additionally, in 30 cases of adrenocortical carcinoma, exons 18-21 of the EGFR gene were cloned and sequenced. EGFR expression was found in 128 of 169 adrenocortical carcinoma samples (76%), and in 60 of these samples ( ¼ 36%) strong membrane staining was detected. However, there was no significant correlation with clinical outcome. In addition, all 30 sequenced cases revealed unmutated EGFR genes. In contrast, only 1 out of 31 adrenocortical adenomas weakly expressed the EGFR (3%). In summary, EGFR was overexpressed in more than three-quarters of adrenocortical carcinoma cases of this series. However, no mutations of the EGFR gene were found and EGFR expression was not of prognostic relevance. As EGFR is hardly expressed in adrenocortical adenomas, our results suggest that its expression in adrenocortical tumors indicates a malignant phenotype, which may be used in the differential diagnosis between adrenocortical adenomas and carcinomas.

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“…Finally, Ocker et al (2000) also did not identify K-Ras mutations in 40 AAs. It is interesting to note that Epidermal Growth Factor Receptor (EGFR) is overexpressed in ACAs as well as in ACCs (Kamio et al, 1990;Sasano et al, 1994). Moreover, as the signal transducing tyrosine kinase activity of the EGFR is mediated by Ras proteins among others, it is conceivable that chronically active wild type Ras promotes M a n u s c r i p t 6 tumorigenesis through activation of multiple Ras effectors that contribute to deregulated cell growth, dedifferentiation, and increased survival, migration and invasion.…”

Section: Specific Genetic Alterations In Sporadic Adrenocortical Tumorsmentioning

confidence: 99%

Insights into the role of genetic alterations in adrenocortical tumorigenesis

Herbet

Feige

Thomas

2009

Molecular and Cellular Endocrinology

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Whereas benign adrenocortical tumors are frequent in the population, adrenocortical carcinoma (ACC) is a rare cancer. Significant advances in the understanding of the pathogenesis of sporadic ACCs have been possible through the study of hereditary syndromes responsible for ACCs. The genetic alterations involved in these syndromes have also been found in sporadic ACCs. Several specific genes have been shown to be altered in sporadic ACCs. Despite these progresses, the underlying sequence(s) of events remains( ) to be elucidated. Progressive transformation of a normal tissue into a benign tumor and ultimately into a carcinoma occurs via accumulation of genetic and epigenetic alterations. Likewise, a multistage model has been proposed for the adrenal tumor development. This review summarizes the molecular alterations likely involved in the multistage tumorigenesis and describes a mouse model which allows us to evaluate the effect of individual genes or combination of genes in the development of adrenocortical tumors.

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Immunohistochemical expression of epidermal growth factor receptors in human adrenocortical carcinoma

Cited by 91 publications

References 28 publications

Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival

Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival

Epidermal growth factor receptor in adrenocortical tumors: analysis of gene sequence, protein expression and correlation with clinical outcome

Insights into the role of genetic alterations in adrenocortical tumorigenesis

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