Promoter methylation of survivin gene in infantile hemangiomas

Abstract

Objective To explore the methylation status of CpG island in survivin gene promoter region in different pathological stages of infantile hemangiomas and normal skin tissues by bisulfite sequencing PCR (BSP) and examine the possible relationship of promoter methylation in survivin gene and the proliferation or involution of infantile hemangiomas. Methods The immunohistochemical method of S-P was used for detecting the expression of survivin protein in paraffin specimens of infantile proliferative hemangioma (n=30), involuting hemangioma (n=30) and normal foreskin tissues (n=10); tissue genomic DNA was extracted from paeaffin embedding. After purification, the method of BSP was employed for detecting the methylation status of CpG island in survivin gene promoter region of proliferative hemangioma (n=30), involuting hemangioma (n=30) and normal foreskin tissues (n=10). Results The positive expression rates of survivin protein in proliferative hemangiomas involuting hemangiomas and normal foreskin tissues were 76.6%(23/30), 33.3% (10/30) and 20% (2/10) respectively. Among 10 cases of normal foreskin tissues, only 1 case (10%) of CpG island was demethylated in survivin gene promoter while 9 cases (90%) were methylated; among 30 cases of involuting hemangiomas, 8 cases (26.6%) of CpG island were demethylated in survivin gene promoter while 22 cases (73.3%) were methylated; among 30 cases of proliferative hemangiomas, 24 cases (80.0%) of CpG island were demethylated in survivin gene promoter and 6 cases (20%) were methylated; The demethylated rate of CpG island in survivin gene promoter was significantly lower in proliferative hemangiomas than those in involuting hemangiomas and normal foreskin tissues. CpG island in survivin gene promoter non-methylated expressed survivin protein in 31/33 hemangiomas while CpG island in survivin gene promoter methylated did not express survivin protein in 26/27 hemangiomas. Conclusions The expression of survivin protein is significantly greater in proliferative hemangiomas than that in involuting hemangiomas. The methylation status of CpG island in survivin gene promoter has significant differences among proliferative hemangiomas, involuting hemangiomas and normalforeskin tissues. The methylation status of survivin gene promoter is correlated with the expression of survivin protein in hemangiomas. And aberrant methylation of CpG island in survivin gene promoter region may play a role in the proliferation and involution of hemangiomas. Key words: Hemangioma; Survivin; Methylation