Cutaneous Melanoma: A Review of Multifactorial Pathogenesis, Immunohistochemistry, and Emerging Biomarkers for Early Detection and Management

Abstract

Cutaneous melanoma (CM) is an increasingly significant public health concern. Due to alarming mortality rates and escalating incidence, it is crucial to understand its etiology and identify emerging biomarkers for improved diagnosis and treatment strategies. This review aims to provide a comprehensive overview of the multifactorial etiology of CM, underscore the importance of early detection, discuss the molecular mechanisms behind melanoma development and progression, and shed light on the role of the potential biomarkers in diagnosis and treatment. The pathogenesis of CM involves a complex interplay of genetic predispositions and environmental exposures, ultraviolet radiation exposure being the predominant environmental risk factor. The emergence of new biomarkers, such as novel immunohistochemical markers, gene mutation analysis, microRNA, and exosome protein expressions, holds promise for improved early detection, and prognostic and personalized therapeutic strategies.

PRAME Updated: Diagnostic, Prognostic, and Therapeutic Role in Skin Cancer

“…Hence, when dealing with a metastatic disease, relying solely on PRAME expression for diagnosing melanoma is insufficient, and confirmation through supplementary immunohistochemical or molecular analyses is essential. Nevertheless, the assessment of PRAME in metastatic melanoma goes beyond diagnostic significance, potentially holding prognostic value and serving as a prospective target for immunotherapy [37]. Regarding mucosal melanocytic lesions, which are less common than cutaneous ones, several studies have focused on detecting the presence of PRAME within these lesions to assess their applicability [34].…”

Inhibiting IL11RA to mitigate hepatic metastasis in skin cutaneous melanoma: Comprehensive insights from in vitro and in vivo investigations

“…Among its various subtypes, skin cutaneous melanoma (SKCM) is the most prevalent, typically arising on sun‐exposed skin areas 1,2 . Despite constituting only 4% of skin cancers, SKCM is responsible for a staggering 75% of skin cancer‐related deaths, underscoring the critical need for early detection and intervention 3 . While advancements have improved outcomes, a subset of patients presents with metastatic disease at diagnosis or later develops metastasis, with the liver being a common site 4,5 .…”

“… 1 , 2 Despite constituting only 4% of skin cancers, SKCM is responsible for a staggering 75% of skin cancer‐related deaths, underscoring the critical need for early detection and intervention. 3 While advancements have improved outcomes, a subset of patients presents with metastatic disease at diagnosis or later develops metastasis, with the liver being a common site. 4 , 5 Liver metastases, occurring in 10%−20% of cutaneous melanoma patients, present unique challenges, emphasizing the urgency for innovative treatment strategies.…”

The Prognostic Value of Proliferative Activity in Cutaneous Melanoma: A Pilot Study Evaluating the Mitotic Rate and Ki67 Index to Predict Patient Outcomes

“…Biomedicines 2024, 12, 1318 2 of 16 An immunohistochemical analysis is a widely used method in evaluating cutaneous melanocytic neoplasms, particularly for diagnosing undifferentiated or dedifferentiated tumors or for distinguishing between severely dysplastic nevi and melanomas. Nevertheless, an immunohistochemical analysis has a limited prognostic value in such cases [8][9][10]. Among the possible predictive markers, the proliferation marker Ki67 requires special attention as it has a proven prognostic significance in certain other malignancies such as breast carcinomas or neuroendocrine neoplasms [11,12].…”