Prognostic impact and concordance of TERT promoter mutation and protein expression in matched primary and metastatic cutaneous melanoma

BACKGROUND: TERT promoter mutations are frequent in melanoma. Here we analysed the concordance and prognostic impact of TERT mutation and telomerase reverse transcriptase (TERT) protein expression in a large melanoma series. METHODS: In 194 primary nodular melanomas with 72 matched loco-regional metastases, TERT promoter mutation status was assessed by Sanger sequencing and TERT protein expression by immunohistochemistry. RESULTS: TERT mutations were found in 68% of primary melanomas and 64% of metastases, and the mutation status was discordant between primary tumour and metastasis in 24% of the cases. 6 of the 10 cases with discordant and wild-type metastases were also TERT wild type when re-tested in other intra-tumour regions, whereas 4 cases were mutation positive. TERT-mutated tumours tended to be thicker, have a higher mitotic count and higher patient age than TERT wild-type cases, but there was no significant association with reduced survival. TERT protein expression did not correlate with mutation status, but showed a similar discordancy between the primary and first metastatic lesion, and was significantly associated with reduced survival. CONCLUSIONS: TERT promoter mutations showed inter- and intra-tumoural discordancy, whereas only expression of TERT protein was associated with reduced patient survival.