Wilson Melissa A, Zhong Judy, Johannet Paul, Lee Yesung, Masub Natasha, Wechter Todd, Moran Una, Berman Russell S, Shapiro Richard L, Weber Jeffrey, Pavlick Anna, Osman Iman
Division of Hematology and Oncology, Department of Medicine, Perlmutter Cancer Center.
Interdisciplinary Melanoma Cooperative Group.
Melanoma Res. 2020 Oct;30(5):492-499. doi: 10.1097/CMR.0000000000000691.
Melanoma disseminates to the skeletal system where it is then difficult to treat. Yet, there remains limited research investigating metastatic bone disease (MBD) in melanoma. Here, we evaluate whether there are distinct clinicopathologic variables at the time of primary melanoma diagnosis that predispose metastases to engraft bone, and we test the hypothesis that patients with MBD have different responses to treatment. Cutaneous melanoma patients enrolled in a prospective database were studied. Individuals with metastatic melanoma and bone metastases (M-Bone) were compared to those with metastatic disease but no M-Bone. Of the 463 (42.7%) patients, 198 with unresectable metastatic melanoma had M-Bone and 98 developed bone metastasis (bone mets) as first site. Progression-free survival and overall survival were significantly worse in patients with M-Bone compared to those without M-Bone (P < 0.001) independent of treatment modalities, and in patients whose melanoma spread to bone first, compared to those who developed first mets elsewhere (P < 0.001). Interestingly, patients with bone mets presented with primary tumors that had more tumor infiltrating lymphocytes (P < 0.001) and less often a nodular histologic subtype compared to patients without M-Bone (P < 0.001). Our data suggest that melanoma bone metastasis is a distinct clinical and biological entity that cannot be explained by generalized metastatic phenotype in all patients. The observed dichotomy between more favorable primary histopathologic characteristics and a grave overall prognosis requires more studies to elucidate the molecular processes by which melanomas infiltrate bone and to build a mechanistic understanding of how melanoma bone metastases yield such detrimental outcomes.
黑色素瘤会扩散至骨骼系统，进而难以治疗。然而，针对黑色素瘤转移性骨病（MBD）的研究仍然有限。在此，我们评估在原发性黑色素瘤诊断时是否存在不同的临床病理变量，这些变量会促使转移灶在骨骼中着床，并且我们检验了MBD患者对治疗有不同反应这一假设。对纳入前瞻性数据库的皮肤黑色素瘤患者进行了研究。将伴有转移性黑色素瘤和骨转移（M-骨）的个体与伴有转移性疾病但无M-骨的个体进行了比较。在463名（42.7%）患者中，198名不可切除的转移性黑色素瘤患者发生了M-骨转移，98名患者以骨转移作为首个转移部位。与无M-骨转移的患者相比，M-骨转移患者的无进展生存期和总生存期显著更差（P<0.001），与治疗方式无关；与首先发生其他部位转移的患者相比，黑色素瘤首先转移至骨的患者情况也是如此（P<0.001）。有趣的是，与无M-骨转移的患者相比，发生骨转移的患者原发性肿瘤的肿瘤浸润淋巴细胞更多（P<0.001），且结节状组织学亚型较少见（P<0.001）。我们的数据表明，黑色素瘤骨转移是一种独特的临床和生物学实体，无法用所有患者的广义转移表型来解释。原发性组织病理学特征较为有利与总体预后严重之间存在的这种二分法，需要更多研究来阐明黑色素瘤浸润骨骼的分子过程，并建立对黑色素瘤骨转移如何产生如此有害结果的机制性理解。
