Updates in diagnostic and prognostic markers for cutaneous melanoma

Introduction: The cutaneous melanoma is an aggressive skin malignant neoplasia with the worst prognosis among other histopathological variants of skin cancer. In Brazil, it is estimated a number of 8.980 new cases for the year 2023, according the Nacional Cancer Institute (INCA). Melanomas are also called beyond pathologists as “the great imitator”, because of its variety of histological subtypes and the capacity of mimic other entities. A great progress has been done in strategies and mechanisms for diagnosticate melanomas and also markers for establish prognosis and predict treatment response. Objective: This study has the objective of review the classic and new markers for diagnostic and prognosis in cutaneous melanoma. Methods: This is a literature review study, based on PubMed articles, which were found through the terms “cutaneous melanoma”, “biomarkers”, “prognosis” and “diagnostic”, with the Boolean operator “and”. The articles were selected through their content to the building of this review. Results: Breslow thickness has been validated as an important predictor of survival in patients with melanoma. The primary tumor Breslow thickness and ulceration define the T-category for cutaneous melanoma staging system (according to AJCC 8th edition). Wei et al. performed a multicenter study to determine the prognostic impact of Breslow thickness in acral melanoma (AM). The survival curves differed significantly among patients with T1, T2, and T3, while the survival outcomes for patients with T3 and T4 AM were comparable. In this study, Breslow thickness has showed prognostic value in patients with localized melanoma, but there was no association between tumor thickness and survival in patients with Breslow thickness >2 mm (T3 or T4). The cell proliferation index through Ki67 has been showed by Tang et al. as potential biomarker for adjuvant chemotherapy indication. Patients with Ki67 ≥ 30% and submitted to adjuvant chemotherapy had better response to treatment compared to those with low Ki-67 expression. Ohsie et al. performed a review of useful immunohistochemical stains for melanoma diagnosis, in which S-100 was considered the most sensitive marker for melanocytic lesions. Others like HMB-45, Melan-A and tyrosinase have good specificity, but not so sensitive as S-100. Ki67 proliferation index remains the most useful marker to distinguish benign from malign melanocytic tumors. Wong et al. in ASCO and SSO guideline considered sentinel lymph node biopsy has been useful for intermediate-thickness melanoma, based on results from a meta-analysis that showed low false-negative rates and high rates of sentinel node detection. Molecular targets are often been studied for melanoma treatment through therapeutic targets. BRAF is the most important therapeutic target and the most frequent genetic alteration in cutaneous melanoma (40-60%). According to Teixido et al. study, BRAF inhibitors, as vemurafenib, have demonstrated remarkable clinical activity in patients with BRAF mutation. Conclusions: Cutaneous melanoma is a diagnostic challenge for clinicians and pathologists around the world. Adjuvant methods of detection of these lesions have been used in last decades, with great improvements. Also, old and new prognostic markers are jointly been responsible for indication of therapies, with significantly results.