Alessi Cristina, Scapulatempo Neto Cristovam, Viana Cristiano R, Vazquez Vinicius de Lima
aDepartment of Dermatology in Medical Clinic 'Alessi e Rocha' and Medical Specialists Ambulatories of Barretos bIEP/CEPOM - Research Institute and Molecular Oncology Research Center cDepartment of Surgery - Melanoma and Sarcoma, Barretos Cancer Hospital, Barretos dDepartment of Pathology of Laboratório Bacchi, Botucatu, São Paulo ePathology Service, Américas Centro Oncológico Integrado, Rio de Janeiro, Brazil.
Melanoma Res. 2017 Dec;27(6):565-572. doi: 10.1097/CMR.0000000000000396.
Regional lymph nodes are affected frequently by melanoma metastasis. Its microenvironment may be associated with tumor progression. We investigated sentinel nodes with and without tumor and negative nodes surrounding positive nodes, looking for patterns related to tumor immune interaction and lymphovascular progression. We quantified programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1, vascular endothelial growth factor (VEGF)-A/VEGF-C expressions in lymph nodes of 103 patients who underwent sentinel lymph node biopsy. Two groups were studied: negative sentinel lymph nodes and positive ones. Negative lymph nodes of sequential lymphadenectomy from positive cases were also studied. Markers were assessed by immunohistochemistry. Results were related to clinical/histological outcomes. VEGF-A/VEGF-C analysis showed higher positivity in metastatic nodes and higher positivity in the surrounding negative nodes from positive cases in comparison with nonmetastatic patients. Programmed cell death-ligand 1, studied only in metastasis, presented high positivity, not associated with prognosis. PD-1 expressions were similar in the groups with a 1% cutoff and higher in the metastasis with a 5% cutoff. Higher VEGF-A expression was related to higher pathological stages. PD-1 expression in the lymph node was associated with higher survival. Other clinical and histopatological variables were not associated with marker expression patterns. VEGF-A and VEGF-C expressions in lymph nodes were associated with the presence of lymph node metastasis. PD-1 expression in the lymph node was related to higher survival rates and this should be explored in the context of adjuvant immunotherapy.
区域淋巴结经常受到黑色素瘤转移的影响。其微环境可能与肿瘤进展相关。我们研究了有无肿瘤的前哨淋巴结以及阳性淋巴结周围的阴性淋巴结，寻找与肿瘤免疫相互作用和淋巴管进展相关的模式。我们对103例行前哨淋巴结活检患者的淋巴结中程序性细胞死亡蛋白1（PD-1）/程序性细胞死亡配体1、血管内皮生长因子（VEGF）-A/VEGF-C的表达进行了量化。研究了两组：阴性前哨淋巴结组和阳性前哨淋巴结组。还研究了阳性病例连续淋巴结清扫术中的阴性淋巴结。通过免疫组织化学评估标志物。结果与临床/组织学结果相关。VEGF-A/VEGF-C分析显示，与非转移患者相比，转移淋巴结中的阳性率更高，阳性病例周围阴性淋巴结中的阳性率也更高。仅在转移灶中研究的程序性细胞死亡配体1呈现高阳性，与预后无关。以1%为临界值时，各组中PD-1表达相似；以5%为临界值时，转移灶中的PD-1表达更高。较高的VEGF-A表达与较高的病理分期相关。淋巴结中的PD-1表达与较高的生存率相关。其他临床和组织病理学变量与标志物表达模式无关。淋巴结中VEGF-A和VEGF-C的表达与淋巴结转移的存在相关。淋巴结中的PD-1表达与较高的生存率相关，这一点应在辅助免疫治疗的背景下进行探索。
