Clinicopathological significance of cyclin D1 expression in Rosai-Dorfman disease

Abstract

Objective: 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.