González-Ruiz Lucía, González-Moles Miguel Ángel, González-Ruiz Isabel, Ruiz-Ávila Isabel, Ramos-García Pablo
Dermatology Service, Ciudad Real General University Hospital, 13005 Ciudad Real, Spain.
School of Dentistry, University of Granada, 18010 Granada, Spain.
Cancers (Basel). 2021 Mar 15;13(6):1314. doi: 10.3390/cancers13061314.
Our objective was to evaluate the prognostic and clinicopathological significance of cyclin D1 (CD1) overexpression/CCND1 amplification in melanomas. We searched studies published before September 2019 (PubMed, Embase, Web of Science, Scopus). We evaluated the quality of the studies included (QUIPS tool). The impact of CD1 overexpression/CCND1 amplification on overall survival and relevant clinicopathological characteristic were meta-analyzed. We performed heterogeneity, sensitivity, small-study effects, and subgroup analyses. Forty-one studies and 3451 patients met inclusion criteria. Qualitative evaluation demonstrated that not all studies were performed with the same rigor, finding the greatest risk of bias in the study confounding domain. Quantitative evaluation showed that immunohistochemical CD1 overexpression had a statistical association with Breslow thickness ( = 0.007; OR = 2.09,95% CI = 1.23-3.57), significantly higher frequency of CCND1/cyclin D1 abnormalities has been observed in the primary tumor compared to distant metastases ( = 0.004), revealed also by immunohistochemical overexpression of the protein ( < 0.001; OR = 0.53,95% CI = 0.40-0.71), while the CCND1 gene amplification does not show association ( = 0.43); while gene amplification, on the contrary, appeared more frequently in distant metastases ( = 0.04; OR = 1.70,95% CI = 1.01-2.85) and not in the primary tumor. In conclusion, CCND1/cyclin D1 upregulation is a common molecular oncogenic alteration in melanomas that probably favors the growth and expansion of the primary tumor. This upregulation is mainly consequence to the overexpression of the cyclin D1 protein, and not to gene amplification.
我们的目的是评估细胞周期蛋白D1（CD1）过表达/CCND1扩增在黑色素瘤中的预后及临床病理意义。我们检索了2019年9月之前发表的研究（PubMed、Embase、Web of Science、Scopus）。我们评估了纳入研究的质量（QUIPS工具）。对CD1过表达/CCND1扩增对总生存期及相关临床病理特征的影响进行了荟萃分析。我们进行了异质性、敏感性、小研究效应和亚组分析。41项研究和3451例患者符合纳入标准。定性评估表明，并非所有研究都以相同的严谨程度进行，发现研究混杂领域存在最大的偏倚风险。定量评估显示，免疫组化CD1过表达与Breslow厚度存在统计学关联（P = 0.007；OR = 2.09，95%CI = 1.23 - 3.57），与远处转移相比，在原发性肿瘤中观察到CCND1/细胞周期蛋白D1异常的频率显著更高（P = 0.004），蛋白质的免疫组化过表达也显示了这一点（P < 0.001；OR = 0.53，95%CI = 0.40 - 0.71），而CCND1基因扩增未显示关联（P = 0.43）；相反，基因扩增在远处转移中出现得更频繁（P = 0.04；OR = 1.70，95%CI = 1.01 - 2.85），而在原发性肿瘤中未出现。总之，CCND1/细胞周期蛋白D1上调是黑色素瘤中常见的分子致癌改变，可能有利于原发性肿瘤的生长和扩展。这种上调主要是细胞周期蛋白D1蛋白过表达的结果，而非基因扩增。
