Department of Dermatology and Centre D'investigation Clinique (CIC), Assistance Publique-Hôpitaux de Paris (AP-HP), Saint Louis Hospital, 75010, Paris, France.
Institut Cochin, Cutaneous Biology Lab, INSERM U1016, UMR8104, Université de Paris, 75014, Paris, France.
Virchows Arch. 2022 Feb;480(2):475-480. doi: 10.1007/s00428-021-03119-0. Epub 2021 May 20.
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, CTNNB1 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.
Wnt/β-catenin 信号通路在黑素细胞生物学中发挥着关键作用，并且可能与黑色素瘤的进展有关。在这项研究中，我们回顾性地研究了一组β-catenin（CTNNB1）突变的黑色素瘤患者的真实队列，这些患者的 CTNNB1 突变与 MAPK 突变（BRAF 或 NRAS）相关或不相关，并分析了他们的临床、组织病理学和分子特征。我们的结果表明，无论是否存在并发的 MAPK 突变，CTNNB1 皮肤原发性黑色素瘤比其 CTNNB1 野生型对应物具有更多的增殖特征（增加的 Breslow 厚度、有丝分裂指数和溃疡）。因此，它们通常会进展到转移阶段。此外，同时存在 CTNNB1 和 MAPK 突变并不一定赋予黑色素瘤深部穿透性痣的表型。总之，这项研究提供了证据，表明黑色素瘤中的 CTNNB1 突变与特定的临床和病理特征相关。
