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

Abstract

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.

Mutational analyses of epidermal growth factor receptor and downstream pathways in adrenocortical carcinoma

“…The observed mutations were also described earlier in lung and colon carcinoma, but the response to EGFR-TKI therapy was not reported (23,24,25). Recently, Adam et al (22) found no mutations in 30 ACCs.…”

“…Until now, only four mutations of the EGFR TK domain have been reported in ACC (21,22). Kotoula et al described four activating EGFR mutations, three missense (c.2168TOC, exon 18, c.2354COA, exon 20, and c.2533GOA, exon 21) and one non-sense mutation (c.2193GOA, exon 19) in 35 ACCs.…”

“…Patients are selected for MABs based on EGFR protein expression on the membrane of the tumour (27). Since the majority of ACCs have neither EGFR nor downstream mutations of KRAS, BRAF or PIK3CA, MABs could be of interest, especially since EGFR protein expression is observed in the majority of ACC (22). However, before the initiation of a clinical trial, the EGFR gene status should be determined as EGFR protein expression does not correlate with response to the EGFR MABs (28,29).…”

Szlaki molekularne w raku kory nadnercza — od wiedzy o sygnalizacji komórkowej do metod diagnostyki i leczenia

“…Apart from transcriptome analyses, one of the most common methods to screen a large number of samples is tissue microarray: it has been widely used for immunohistochemistry studies on adrenocortical tumours [21,34,51,52,67,69,80,168].…”

“…Likewise, epidermal growth factor receptor (EGFR) shows elevated levels in adrenocortical carcinomas [78][79][80][81]. EGFR is a potential malignancy marker, as its expression is significantly higher in carcinomas than in adenomas.…”