The value of peritumoral lymphocyte infiltration in progression free survival in TERT and CHEK2 mutant stage I and II melanoma

Background: The presence of tumour infiltrating lymphocytes is a favourable prognostic factor in cutaneous melanoma. However, conflicting conclusions on peritumoral lymphocytes (TIL), and TERT and CHEK2 mutations in the natural course of Stage I and II melanoma, and their prognostic significance is still controversial.

Aim: The current study's objective have been to compare the TERT and CHEK2 mutation status with peritumoral lymphocytic infiltration and progression free survival in Stage I and II melanoma.

Methods: Altogether, 118 patients who underwent melanoma surgical treatment at the Riga East University Hospital at the stage IA-IIC from 2012 until 2017 were retrospectively enrolled in the study. TERT mutational status was assessed in 118 patients. The C228T (NM_198253.3 (TERT):c.-124C>T) point mutation (chr5; 1,295,228 (−124) upstream of the transcription start codon) and C250T substitution (chr5; 1,295,250 (−146) upstream of the transcription start codon), NM_198253.3(TERT):c.-146C>T and CHEK2, GRCh38/hg38 22q12.1(chr22:27557778-28988149) × 3 was assessed by NGS testing. Results. Patients with TERT mutation had significant worse PFS compared to TERT wild melanoma (HR = 13.8, 95 % C.I = 6.8–31.0; p < 0.0001). In additional, patient with TERT mutation and low TIL had significant better PFS compared to patients with TERT mutation and high TIL infiltration (HR = 4.80; 95 %, C.I = 2.30–7.890, p = 0.002). CHEK2 mutations did not associated with PFS. However, patients with CHEK2 had increased TIL infiltration compared to CHEK2 wild melanoma (p < 0.0001). In addition, the CHEK2 and TERT co-mutant melanoma had worse PFS compared to TERT mutant melanoma (HR = 2.95; 95 %, C.I = 1.85–5.89, p = 0.01), which did not correlate with TIL infiltration.

Conclusion: TERT mutant melanoma characterized by worse PFS compared to TERT wild melanoma. Increased TIL infiltration contributed to the better PFS in TERT mutant melanoma, but did not associate with TERT and CHEK2 co-mutant melanoma.