骨原发性朗格汉斯组织细胞增生症中Cyclin D1的表达及临床意义

Clinicopathological significance of Cyclin D1 expression in primary Langerhans cell histiocytosis of bone

目的探讨骨原发性朗格汉斯组织细胞增生症(Langerhans cell histiocytosis,LCH)中Cyclin D1的表达及临床意义。方法回顾性分析21例骨原发性LCH的临床病理学特征,利用免疫组化法检测Cyclin D1、BRAF、p-ERK蛋白的表达,采用Spearman相关分析研究三者之间的关系。采用χ^2检验比较LCH病例与对照组(朗格汉斯细胞微脓肿、皮肤苔藓样病变和皮肤色素沉积症)中Cyclin D1的表达差异。采用ROC曲线法分析不同临床病理参数与不良预后事件的关系。结果21例LCH均呈典型的组织形态学特征。LCH组与对照组中Cyclin D1阳性率分别为100%和3.6%,LCH组中Cyclin D1的表达显著高于对照组(P<0.001)。Spearman相关分析显示:Cyclin D1与BRAF、p-ERK的表达均无相关性,BRAF、p-ERK的表达亦无相关性(P>0.05)。ROC曲线分析发现:核分裂象、Ki-67、Cyclin D1、p-ERK对提示患者不良预后有一定的参考价值(AUC>0.5,P<0.05)。结论Cyclin D1对鉴别LCH和反应性朗格汉斯细胞增生是一个有效的标志物,并能够提示患者的不良预后,其弥漫一致的表达可能与MAPE/ERK通路激活有关。

Purpose To study the clinicopathological value of Cyclin D1 expression in primary Langerhans cell histiocytosis(LCH)of bone.Methods Twenty-one LCHs were evaluated by clinicopathological and immunohistochemical analyses retrospectively.The expression of Cyclin D1,BRAF and p-ERK proteins was detected by immunohistochemistry.The comparisons among the three proteins were performed using Spearman correlation.The expression of Cyclin D1 between the LCH group and the control group(including Langerhans cell microabscess,skin lichenoid lesions and skin pigmentation)were compared by Chi-square test.The relationships between different clinicopathological parameters and adverse prognostic events were analyzed by ROC curve.Results All 21 LCHs showed typical morphological characteristics.The positive rate of Cyclin D1 in the LCH group was 100%,which were significantly higher than that of the control group(3.6%,P<0.001).Spearman correlation analysis showed that the expression of BRAF,p-ERK and Cyclin D1 was not correlated in each comparison(P>0.05).ROC curve analysis showed that mitotic figures,Ki-67,Cyclin D1 and p-ERK had a certain reference value for adverse prognostic events(AUC>0.5,P<0.05).Conclusion Cyclin D1 is a useful marker for distinguishing LCH from reactive Langerhans cells,which can also indicate an adverse prognostic event.Its diffuse and consistent strong expression may be related to the activation of MAPK pathway,but the exact mechanism needs to be further studied.