cyclin D1在Rosai-Dorfman病中表达的临床病理意义
Clinicopathological significance of cyclin D1 expression in Rosai-Dorfman disease
摘要目的:探讨cyclin D1在Rosai-Dorfman病(RDD)中表达的临床病理意义。方法:17例RDD患者行HE和免疫组织化学染色及分子遗传学检测,比较cyclin D1在RDD以及包括29例反应性组织细胞增生、9例IgG4相关性疾病和2例Erdheim-Chester病在内的对照组中的表达。结果:cyclin D1 在RDD(17/17)、反应性组织细胞增生(11/29)、IgG4相关性疾病(3/9)、Erdheim-Chester病(2/2)中表达,表现为RDD细胞或增生的组织细胞核阳性着色。卡方检验显示,cyclin D1的表达在RDD中显著高于反应性组织细胞增生和IgG4相关性疾病( P<0.01),而与Erdheim-Chester病中的表达差异无统计学意义( P>0.05)。利用受试者工作特征曲线(ROC曲线)重新计算cyclin D1的阳性细胞数百分比的表达阈值为27.5%, 曲线下面积(AUC)为0.981( P<0.01)。染色体荧光原位杂交检测CCND1基因未出现重排,仅部分RDD细胞出现拷贝数增加。扩增阻滞突变系统PCR检测KRAS、BRAF、NRAS基因没有检测到任何突变。 结论:cyclin D1可以作为RDD病理诊断的一个辅助指标,其表达可能与MAPK通路激活有关,但其在RDD发病机制中的作用有待进一步研究。
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abstractsObjective:To study the clinicopathological significance of cyclin D1 expression in Rosai-Dorfman disease (RDD).Methods:Seventeen cases of RDD were evaluated by HE, immunohistochemical staining and molecular genetic analysis. Expression of cyclin D1 was compared between RDDs and control group that included 29 cases of reactive histiocytosis, 9 cases of IgG4-related disease, and 2 cases of Erdheim-Chester disease.Results:Cyclin D1 was expressed in RDDs (17/17), reactive histiocytosis (11/29), IgG4-related diseases (3/9), and Erdheim-Chester disease (2/2), respectively, with nuclear staining in the RDD cells or proliferative histiocytes. Chi-square test showed that expression of cyclin D1 was significantly higher in RDDs than in reactive histiocytosis and IgG4-related diseases ( P<0.01), but not in Erdheim-Chester diseases ( P>0.05). The expression threshold for recalculating the percentage of cyclin D1 positive cells was 27.5% (AUC=0.981 , P<0.01) by ROC curve. However, CCND1 gene had no rearrangement detected by fluorescence in situ hybridization, but with increased copies of gene in some RDD cells. ARMS-PCR analysis also did not detect KRAS, BRAF and NRAS gene mutations in any cases. Conclusions:Cyclin D1 may serve as an additional diagnostic marker for RDDs. Its high expression may be related to activation of MAPK pathway, but the pathogenetic significance of cyclin D1 in RDDs needs further study.
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