Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
University of Zurich, Zurich, Switzerland.
Histopathology. 2020 Sep;77(3):460-470. doi: 10.1111/his.14139. Epub 2020 Jul 4.
Despite their low individual metastatic potential, thin melanomas (≤1 mm Breslow thickness) contribute significantly to melanoma mortality overall. Therefore, identification of prognostic biomarkers is particularly important in this subgroup of melanoma. Prompted by preclinical results, we investigated cyclin D1 protein and Ki-67 expression in in-situ, metastatic and non-metastatic thin melanomas.
Immunohistochemistry was performed on 112 melanoma specimens, comprising 22 in situ, 48 non-metastatic and 42 metastatic thin melanomas. Overall, epidermal and dermal cyclin D1 and Ki-67 expression were semiquantitatively evaluated by three independent investigators and compared between groups. Epidermal Ki-67 expression did not differ statistically in in-situ and invasive melanoma (P = 0.7). Epidermal cyclin D1 expression was significantly higher in thin invasive than in in-situ melanoma (P = 0.003). No difference was found in cyclin D1 expression between metastatic and non-metastatic invasive tumours. Metastatic and non-metastatic thin melanomas did not show significant differences in epidermal expression of Ki-67 and cyclin D1 (P = 0.148 and P = 0.611, respectively). In contrast, strong dermal expression of Ki-67 was more frequent in metastatic than non-metastatic samples (28.6 versus 8.3%, respectively, P = 0.001). The prognostic value of dermal Ki-67 expression was confirmed by multivariate analysis (P = 0.047).
We found an increased expression of cyclin D1 in invasive thin melanomas compared to in-situ melanomas, which supports a potential role of this protein in early invasion in melanoma, as suggested by preclinical findings. Moreover, our results confirm that high dermal Ki-67 expression is associated with an increased risk of development of metastasis in thin melanoma and could possibly serve as a prognostic biomarker in clinical practice, especially if combined with additional methods.
尽管单个转移潜能较低，但是厚度≤1mm 的薄型黑素瘤（Breslow 厚度）对黑素瘤总死亡率的影响却很大。因此，在这个黑素瘤亚组中，确定预后生物标志物尤为重要。受临床前结果的启发，我们研究了原位、转移性和非转移性薄型黑素瘤中的细胞周期蛋白 D1 蛋白和 Ki-67 表达。
对 112 个黑素瘤标本进行了免疫组织化学染色，包括 22 个原位、48 个非转移性和 42 个转移性薄型黑素瘤。三位独立的观察者通过半定量评估评估了表皮和真皮中的细胞周期蛋白 D1 和 Ki-67 表达，并比较了各组之间的差异。在原位和侵袭性黑素瘤中，表皮 Ki-67 表达无统计学差异（P=0.7）。在薄型侵袭性黑素瘤中，表皮细胞周期蛋白 D1 表达明显更高（P=0.003）。在转移性和非转移性侵袭性肿瘤中，细胞周期蛋白 D1 表达无差异。在 Ki-67 和细胞周期蛋白 D1 的表皮表达方面，转移性和非转移性薄型黑素瘤之间无显著差异（P=0.148 和 P=0.611）。相比之下，在转移性样本中，Ki-67 在真皮中的强表达更为常见（分别为 28.6%和 8.3%，P=0.001）。多变量分析证实了真皮 Ki-67 表达的预后价值（P=0.047）。
与原位黑素瘤相比，侵袭性薄型黑素瘤中细胞周期蛋白 D1 的表达增加，这支持了该蛋白在黑素瘤早期侵袭中的潜在作用，正如临床前研究结果所表明的那样。此外，我们的结果证实，真皮 Ki-67 表达升高与薄型黑素瘤中转移发展的风险增加相关，并且如果与其他方法结合使用，可能成为临床实践中的一种预后生物标志物。
