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.
To determine if a rank order (RO) would be established among a group of 5 female squirrel monkeys, 14 behaviors were observed and performance in water dominance tests was recorded. Significant positive RO correlations were found between active contact and chasing, and between urine-washing and closed genital display. Significant negative RO correlations were found between active contact and huddling, and between chasing and huddling. The RO determined from the results of the water dominance tests was unstable. It was concluded that the communication system in a subadult female squirrel monkey colony could not be described in terms of a linear RO.
21025 Background: Adrenocortical carcinoma (ACC) is a rare malignancy with incompletely understood pathogenesis and poor prognosis. Overexpression of epidermal growth factor receptor (EGFR) has been demonstrated in several tumors and is partly associated with a more aggressive phenotype and a worse prognosis. In addition, targeting the EGFR tyrosine kinase represents a successful new therapeutic strategy, e.g. in non-small cell lung cancer. Therefore, we investigated the role of EGFR in ACC as a potential therapeutic target. Methods: EGFR expression was analyzed by immunohistochemistry in 115 ACCs and 5 normal adrenals using paraffin sections and tissue arrays (scoring of expression: 0–3). Utilizing the clinical data from the German ACC registry, Kaplan Meier survival analyses were performed. In 30 patients the tumor DNA was sequenced for mutations of the “hot spot” exons 19–21 of the EGFR gene. In addition, cells of the ACC cell line NCI-h295 were incubated with the EGFR antibody cetuximab (1–100 μg/ml) and cell proliferation was measured by MTT tests. Results: Immunohistochemistry revealed EGFR expression in 78% of ACCs. In 67/115 (58%) of the ACCs and 0/5 of the normal adrenals the expression level was judged as moderate-to-high (score 2 or 3). However, the expression level did not correlate with the clinical outcome in these patients. In addition, none of the sequenced tumor DNA samples showed a mutation in exons 19–21. Cetuximab exhibited a dose dependent antiproliferative effect in NCI-H295 cells (cell viability: 1μg/ml: 95±2%; 10μg/ml 90±3%*; 100 μg/ml 85±4%* vs untreated control cells: 100±3%; * = p<0.01). Conclusion: EGFR is overexpressed in the majority of ACC. Moreover, in vitro experiments demonstrated that inhibition of EGFR signalling lead to moderate growth inhibition in ACC cells. Therefore, in patients with ACC refractory to established cytotoxic therapies the experimental use of EGFR inhibitors (combined with cytotoxic therapy) seems to be justified. No significant financial relationships to disclose.
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