Chemokine receptor 7 is highly expressed in the adrenal cortex and in benign and malignant adrenocortical tumours but does not show prognostic relevance in adrenal cancer

Introduction: The chemokine receptor CCR7 and its ligands CCL19 and CCL21 are involved in the regulation of immune function by guiding cells to and within lymphoid organs. CCR7 has further been reported as a key factor of epithelial-mesenchymal transition and metastasis in different types of cancer. So far no data exist on the expression of CCR7 in adrenocortical tumours.

Methods: CCR7 expression was investigated by quantitative real-time PCR and western blot in nine ACCs, two normal human adrenal glands and the human adrenocortical cancer cell line NCI-h295. Protein expression was furthermore quantified in tissue samples of 136 adrenocortical tumors (80 primary adrenocortical carcinomas (ACC), 11 local recurrences of ACC, 11 ACC metastases, 12 non functioning adenomas (NFA), 11 cortisol producing adenomas (CPA), and 11 aldosterone producing adenomas (APA)) by immunhistochemistry. Correlation analysis was performed for CCR7 expression scores, known prognostic factors (Ki67, Weiss score) and disease free and overall survival.

Results: CCR7 was found to be expressed in normal adrenals, adrenocortical tumours and NCI-h295 cells. In the normal adrenal cortex CCR7 was mainly localized in the outer zones. No significant differences in CCR7 membrane expression could be found between primary tumours, local recurrences and metastases of ACC (H-scores: 1.7 ± 0.9; 2.3 ± 0.7; 1.7 ± 0.4, respectively). No significant correlation was seen for Ki67, Weiss score or survival. Highest CCR7 expression was noted in NFAs (H-score 2.5 ± 0.6) which was significantly higher compared to primary ACC, CPA and APA. Lowest expression levels were seen in APAs (H-score 1.1 ± 0.8).

Conclusion: CCR7 is expressed in the normal adrenal cortex and in benign and neoplastic adrenal tissue. In the current cohort of ACC patients no differences in CCR7 protein expression levels could be observed between primary ACC and distant metastases of ACC. Furthermore, CCR7 expression was not found to be correlated with survival. The exact physiological role in the adrenal cortex and the pathophysiological relevance in ACC is subject of further investigation.