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Clinicopathologic and molecular characterization of melanomas mutated for CTNNB1 and MAPK

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Abstract

Wnt/β-catenin signaling plays crucial roles in melanocyte biology and may be implicated in melanoma progression. In this study, we retrospectively examined a real-life cohort of melanomas mutated for β-catenin (CTNNB1), in association or not with a MAPK mutation (of BRAF or NRAS), and analyzed their clinical, histopathological, and molecular characteristics. Our results indicate that, regardless of the presence of a concurrent MAPK mutation, CTNNB1mut cutaneous primary melanomas display more proliferative hallmarks (increased Breslow thickness, mitotic index, and ulceration) than their CTNNB1 wild-type counterparts. Accordingly, they often progress to the metastatic stage. Furthermore, concurrent CTNNB1 and MAPK mutations do not necessarily confer a deep penetrating nevi phenotype. Altogether, this study provides evidence that CTNNB1 mutations in melanomas are associated with specific clinical and pathological features.

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Fig. 1
Fig. 2

Data availability

All data that support the conclusions are available from the authors on request.

Abbreviations

ALM:

Acral lentiginous melanoma

CTNNB1:

β-Catenin

CR:

Complete response

DPN:

Deep penetrating nevus

DPNM:

Deep penetrating nevus-like melanoma

TIL:

Tumor-infiltrating lymphocytes

LMM:

Lentigo maligna melanoma

MAPK:

Mitogen-activated protein kinase

mut:

Mutated

NA:

Not applicable

NGS:

Next-generation sequencing

NM:

Nodular melanoma

PD:

Progressive disease

PR:

Partial response

SSM:

Superficial spreading melanoma

wt:

Wild-type

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Acknowledgements

The authors would like to thank all members of the dermato-oncology medical team of Saint Louis Hospital working with melanoma patients.

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Author notes

  1. Bénédicte Oulès

    Present address: Department of Dermatology, Assistance Publique-Hôpitaux de Paris (AP-HP), Cochin Hospital, 75006, Paris, France

Authors and Affiliations

  1. Department of Dermatology and Centre D’investigation Clinique (CIC), Assistance Publique-Hôpitaux de Paris (AP-HP), Saint Louis Hospital, 75010, Paris, France

    Bénédicte Oulès, Barouyr Baroudjian, Julie Delyon & Céleste Lebbé

  2. Institut Cochin, Cutaneous Biology Lab, INSERM U1016, UMR8104, Université de Paris, 75014, Paris, France

    Bénédicte Oulès

  3. Department of Pharmacology and Tumor Genomics, Assistance Publique-Hôpitaux de Paris (AP-HP), Saint Louis Hospital, 75010, Paris, France

    Samia Mourah, Fanélie Jouenne, Baptiste Louveau & Aurélia Gruber

  4. Université de Paris, INSERM UMRS 976, 75010, Paris, France

    Samia Mourah, Fanélie Jouenne, Julie Delyon, Baptiste Louveau, Aurélia Gruber, Céleste Lebbé & Maxime Battistella

  5. Department of Pathology, Assistance Publique-Hôpitaux de Paris (AP-HP), Saint Louis Hospital, 75010, Paris, France

    Maxime Battistella

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Contributions

M.B. conceived the study and designed the experiments. B.O., S.M., B.B., F.J., J.D., B.L., A.G., C.L., and M.B. collected data, performed experiments, and analyzed data. B.O. and M.B. wrote the manuscript with input from all the authors.

Corresponding author

Correspondence to Maxime Battistella.

Ethics declarations

This study was performed after establishing the absence of registered opposition to the use of clinical and pathological data and tissue samples in accordance with French Bioethics Law for retrospective noninterventional research studies.

Conflict of interest

The authors declare no conflict of interest regarding the publication of this article. B.O. declares grants to attend congresses from Novartis and BMS. A.G. and F.J. declare no conflict of interest. C.L. declares a consulting role for Amgen, BMS, MSD, Novartis, and Roche, research funding from BMS and Roche, honoraria from Amgen, BMS, Incyte, MSD, Novartis, Pfizer, Pierre Fabre and Roche, and travel accommodations from BMS. S.M. declares a consulting role for Novartis, Biocartis, and Roche and research funding from Biocartis. M.B. declares honoraria from Innate Pharma, Takeda, BMS, and Leo Pharma.

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Supplementary Table 1

Genes targeted in the customized NGS panel (XLSX 12 KB)

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Oulès, B., Mourah, S., Baroudjian, B. et al. Clinicopathologic and molecular characterization of melanomas mutated for CTNNB1 and MAPK. Virchows Arch 480, 475–480 (2022). https://doi.org/10.1007/s00428-021-03119-0

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  • DOI: https://doi.org/10.1007/s00428-021-03119-0

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