Altered expression of cell cycle regulators Cyclin D1, p14, p16, CDK4 and Rb in nodular melanomas.
Altered expression of cell cycle regulators Cyclin D1, p14, p16, CDK4 and Rb in nodular melanomas.
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结节性黑色素瘤中细胞周期调节因子 Cyclin D1、p14、p16、CDK4 和 Rb 的表达发生改变。
DOI：
10.3892/ijo.25.6.1559
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发表时间：
2004
影响因子：
5.2
通讯作者：
L. Akslen
中科院分区：
文献类型：
--
作者：
Ingeborg M. Bachmann;O. Straume;L. Akslen
细胞周期调节蛋白在肿瘤发展中起重要作用。为了研究Cyclin D1、p14、CDK4和Rb的改变是否与恶性黑色素瘤的肿瘤细胞增殖、肿瘤进展和患者生存相关，我们检测了202例垂直生长期肿瘤和68例相应转移瘤中Cyclin D1、p14、CDK4和Rb的表达，并将结果与Ki-67表达、p16和p53表达、临床病理变量和生存数据进行了比较。35%的病例中Cyclin D1的核染色强烈，与Rb水平高相关（p=0.05），但与生存或其他标志物检测无关。在63%的结节性黑色素瘤中发现p14的强染色，并与p53的强表达（p=0.014）和CDK4的高水平（p<0.0001）相关。低p14表达与肿瘤厚度增加（p=0.008）和侵袭水平增加（p=0.020）相关。在81%的病例中发现了CDK4的强核染色，并且与肿瘤厚度低于中位数3.7 mm和生存率提高相关（log-rank检验，p=0.024）。此外，56%的肿瘤显示强烈的Rb核染色，这些病例与p16染色缺失/低水平（p=0.030）， p14高水平（p=0.010）以及Ki-67高表达（p=0.005）显著相关。我们的研究结果似乎证实了p16-Rb通路在垂直生长期黑色素瘤的肿瘤进展和预后中起重要作用，而p14-p53通路的改变可能不太重要。
Cell cycle regulating proteins are important in tumour development. To investigate whether alterations in Cyclin D1, p14, CDK4 and Rb are associated with tumour cell proliferation, tumour progression and patient survival in malignant melanoma, we examined 202 vertical growth phase tumours and 68 corresponding metastases for expression of Cyclin D1, p14, CDK4 and Rb, and compared the results with Ki-67 expression, p16 and p53 expression, clinico-pathological variables, and survival data. Nuclear staining of Cyclin D1 was strong in 35% of cases, and correlated with high levels of Rb (p=0.05), but not with survival or other markers tested. Strong staining of p14 was found in 63% of nodular melanomas and was associated with strong p53 expression (p=0.014), and with high levels of CDK4 (p<0.0001). Low p14 expression was associated with increased tumour thickness (p=0.008) and increasing level of invasion (p=0.020). Strong nuclear staining for CDK4 was found in 81% of cases and was associated with tumour thickness below the median value of 3.7 mm and improved survival (log-rank test, p=0.024). Further, 56% of the tumours showed strong nuclear staining for Rb, and these cases were significantly associated with absent/low levels of p16 staining (p=0.030), high levels of p14 (p=0.010), as well as high Ki-67 expression (p=0.005). Our results seem to confirm that the p16-Rb pathway plays an important role in tumour progression and prognosis in vertical growth phase melanomas, whereas alterations in the p14-p53 pathway might be less important.