A biomarker panel predicts recurrence-free survival in ulcerated primary cutaneous melanoma

Abstract

Background: Ulceration is an independent adverse prognostic factor in cutaneous malignant melanoma (CMM). There is, however, a need for additional prognostic markers to identify patients with ulcerated stage I-II CMM who have a high-risk for recurrence. The aim of this study was to examine the prognostic impact of BRAF mutation, proliferation and presence of tumour infiltrating lymphocytes (TILs) in primary ulcerated CMM.

Material and methods: We have used a consecutive cohort consisting of 71 primary ulcerated CMM (T1b-T4b). BRAF mutation was detected using Cobas test and pyrosequencing. Protein expression of the proliferation marker Ki67 was analysed using immunohistochemistry. Presence of TILs was evaluated in representative hematoxylin-eosin stained formalin-fixed paraffin-embedded tumour sections.

Results: Proportion of BRAF mutated alleles, proliferation and presence of TILs all had a statistically significant impact on recurrence free survival in univariate analyses (HR 2.44, 95% CI 1.23-4.84, p = 0.011; HR 2.66, 95% CI 1.32-5.35, p = 0.006 respectively HR 0.48, 95% CI 0.24-0.98, p = 0.045). A trend test found a statistically significant decrease in the proportion of recurrence by including the three favourable factors (BRAF wildtype/low proportion of BRAF mutated alleles, low proliferation and high presence of TILs) (p = 0.0004). When at least two out of three factors were present there was a statistically significant association with longer recurrence free survival in the multivariate analysis (HR 0.30, 95% CI 0.15-0.61, p = 0.001) when adjusted for Breslow thickness, an established independent prognostic marker for CMM.

Conclusion: Thus, this panel of markers could be an interesting novel concept for predicting the clinical outcome in patients with high-risk stage I-II ulcerated CMM.

Keywords: BRAF; Ki67; TILs; prognosis; ulcerated primary melanoma.