A paradigm shift in understanding vulvovaginal melanoma as a distinct tumor type compared with cutaneous melanoma.
Gynecol Oncol
; 188: 13-21, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-38861917
ABSTRACT
OBJECTIVE:
Our goal was to compare molecular and immune profiles of vulvovaginal melanoma (VVM) with cutaneous melanoma (CM) and explore the significance of immune checkpoint inhibitor (ICI) agents on survival.METHODS:
Samples from VVM and CM tumors underwent comprehensive molecular and immune profiling. Treatment and survival data were extracted from insurance claims data and OS was calculated from time of ICI treatment to last contact. Statistical significance was determined using chi-square and Wilcoxon rank sum test and adjusted for multiple comparisons.RESULTS:
Molecular analysis was performed on 142 VVM and 3823 CM tumors. VVM demonstrated significantly (q < 0·01) less frequent BRAF and more frequent KIT, ATRX, and SF3B1 mutations. Alterations in pathways involving DNA damage and mRNA splicing were more common in VVM, while alterations in cell cycle and chromatin remodeling were less common. Immunogenicity of VVM was lower than CM, with an absence of high TMB (0% vs 46.9%) and lower PD-L1 positivity (18·0% vs 29·5%). Median immune checkpoint gene expression was lower in VVM, as were cell fractions for type I macrophages and CD8+ T-cells(q < 0·01). Myeloid dendritic cells were increased in VVM(q < 0·01). Median OS was shorter for VVM than for CM patients treated with ICIs (17·6 versus 37·9 months, HR1·65 (95% CI 1·02-2·67) p = 0·04).CONCLUSIONS:
VVM has a distinct molecular and immune profile compared to CM, which may contribute to the worse survival in VVM compared to CM patients treated with ICI therapy. Though ICIs have been a mainstay of treatment in recent years, our findings suggest that new therapeutic strategies are needed.Palabras clave
Texto completo:
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Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
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Neoplasias Vaginales
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Neoplasias de la Vulva
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Inhibidores de Puntos de Control Inmunológico
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Melanoma
Límite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Año:
2024
Tipo del documento:
Article