Expression of telomerase (hTERT) in aldosterone-producing adrenocortical tumors

Abstract

Telomerase was found in cancers and immortalized cell lines, but only occasionally in normal tissues, thus suggesting that measurement of its hTERT subunit might help distinguishing benign from malignant tumors. Data on hTERT expression in adrenocortical tumors are scant and mostly confined to non-functioning tumors. Therefore, we investigated whether hTERT expression may predict malignancy in aldosterone producing adrenocortical tumors. We measured hTERT mRNA with a real-time one-step reverse transcription (RT) polymerase chain reaction (PCR) method, based on the use of hTERT-specific fluorescence resonance energy transfer (FRET) probes, in 19 adrenalectomized patients with aldosterone-producing adenomas (APAs), in whom long-term follow-up (median 7 years, range 5-14 years) data were available. We also studied two rare aldosterone-producing carcinomas (APCs), eight adrenocortical carcinomas (ACs), twelve normal adrenal cortexes, and two malignant cell lines (NCI-295H and SW-13). Telomerase activity and hTERT immunoreactivity were also investigated. Of interest, we detected hTERT mRNA in 58% of APAs at levels similar to those of malignant tumors, which all consistently showed hTERT expression. In hTERT expressing tumors, immunocytochemistry showed the nuclear expression of hTERT. No hTERT expression was found in the normal adrenocortical tissue. No histopathology differences were observed between hTERT-positive and -negative APAs; however, a patient originally held to have an hTERT-positive APA was retrospectively classified as APC because of metastatic spread. In conclusion, RT-PCR measurement of hTERT mRNA is a hallmark of malignant adrenocortical tumors, but identifies also a subset of hTERT-expressing APAs that might show metastatic spread at long-term follow-up.