Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Centro Studi GISED, Bergamo, Italy.
PLoS One. 2018 Nov 8;13(11):e0207019. doi: 10.1371/journal.pone.0207019. eCollection 2018.
Finding new markers to assess prognosis of melanoma without the necessity to perform a surgical interventions is an important goal in melanoma research. The current study aimed to assess the correlation of clinical course and prognosis of primary and metastatic melanoma with expression of VEGF family and their receptors.
A ngTMA block was made from the randomly selected paraffin tissue blocks of the patients with melanocytic nevi, primary and metastatic melanoma. Then sections cut from ngTMA-block were immunohistochemically stained with proper antibodies. Expression of these proteins was investigated using automated image analysis and compared among the study groups.
We analyzed the tissue of 238 patients with following diagnoses: 101 (42.4%) with a diagnosis of nevus, 86 (36.1%) Malignant melanoma and 51 (21.4%) metastasis. Median follow-up time for the malignant lesions was 5.71 years. Among the tested antigen, VEGF-C (p = 0.016), VEGF-R2 (p<0.001) and VEGF-R3 (p = 0.002) were significantly higher expressed in the metastatic tissues. When these scores were assessed in multiple regression models, the only independent factor linked to patient's diagnosis was VEGF-R2 (p<0.001). In addition, groups of highly correlated variables (VEGF-C and VEGF-R3, VEGF-A and VEGF-R1) were found to form separate sub-clusters. On the other side, high values of VEGF-C were associated with both overall and disease-free survival with a statically significant HR of 2.76 (95% CI: 1.27, 5.98; p = 0.01) and 2.82 (95%CI: 1.62, 4.91; p<0.001), respectively.
This study shows that VEGF-C and VEGF-R2 might represent new prognostic marker in MM. However, further prospective studies are warranted to test their real efficacy as a prognostic marker.
寻找新的标志物来评估黑色素瘤的预后而无需进行手术干预是黑色素瘤研究的一个重要目标。本研究旨在评估血管内皮生长因子（VEGF）家族及其受体的表达与原发性和转移性黑色素瘤的临床过程和预后的相关性。
从黑色素细胞痣、原发性和转移性黑色素瘤患者的随机选择的石蜡组织块中制作了一个 AngTMA 块。然后，从 ngTMA 块中切下的切片用适当的抗体进行免疫组织化学染色。使用自动图像分析研究这些蛋白质的表达，并在研究组之间进行比较。
我们分析了 238 名患者的组织，其中包括以下诊断：101 名（42.4%）患有痣，86 名（36.1%）患有恶性黑色素瘤和 51 名（21.4%）患有转移瘤。恶性病变的中位随访时间为 5.71 年。在测试的抗原中，VEGF-C（p = 0.016）、VEGF-R2（p<0.001）和 VEGF-R3（p = 0.002）在转移性组织中表达明显更高。当在多变量回归模型中评估这些评分时，唯一与患者诊断相关的独立因素是 VEGF-R2（p<0.001）。此外，发现高相关性变量组（VEGF-C 和 VEGF-R3、VEGF-A 和 VEGF-R1）形成单独的亚群。另一方面，高 VEGF-C 值与总生存期和无病生存期相关，HR 值分别为 2.76（95%CI：1.27，5.98；p = 0.01）和 2.82（95%CI：1.62，4.91；p<0.001）。
本研究表明，VEGF-C 和 VEGF-R2 可能是 MM 的新预后标志物。然而，需要进一步的前瞻性研究来测试它们作为预后标志物的实际效果。
