糖皮质激素受体亚型在皮肤血管瘤和血管畸形中的表达

Jiang Xue-wu, Wang Guang-huan, Li Jian-hong, Chen Zhong-xian, He Fei

Department of Pediatric Surgery, Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, China.

Chin Med J (Engl). 2005 Jun 20;118(12):977-81.

BACKGROUND

Hemangiomas are the most common tumors in children. Some hemangiomas may require intervention because of their location, size, behavior, or potential for important complications. Pharmacological therapy with glucocorticoids is the mainstay treatment, but there is no consensus on therapeutic regimens or candidate selection, therapeutic efficacy varies, and the mechanism mediating the beneficial effects of glucocorticoids remains unclear. This study was performed to investigate the expression patterns of the glucocorticoid receptor (GR) and its alpha isoform (GRalpha) in cutaneous hemangiomas and vascular malformations.

METHODS

SP immunohistochemical technique was used to examine the expression of GR(e-20) (GR) and GR(p-20) (GRalpha) on vascular endothelial cells in 80 specimens that included 33 proliferating hemangiomas, 32 involuting hemangiomas, 7 vascular malformations as well as 8 normal skin tissues, all obtained from infants and children. GR and GRalpha expression in prepared tissue slides were examined using automated computer-assisted microscopic analysis. Mean gray scale values were compared among the various tumor types.

RESULTS

The mean gray scale values of GR were 127.0 +/- 6.4 and 121.4 +/- 6.6 in hemangiomas and vascular malformations respectively, but this difference was not statistically significant (P = 0.104). However, these values were all markedly higher than that of normal skin, which was only 108.6 +/- 6.8 (P = 0.001 and P = 0.000 for comparison with hemangiomas and vascular malformations respectively). The gray scale of GR in proliferation and involuting hemangiomas were 127.9 +/- 4.8 and 126.0 +/- 5.8 respectively, but this difference was not significant (P = 0.146). However, GRalpha expression in hemangiomas, vascular malformations and normal skin declined gradually in stepwise fashion (127.3 +/- 5.4, 120.4 +/- 6.1 and 109.9 +/- 5.3 respectively; P < 0.001). GRalpha expression was higher in proliferating hemangiomas than in involuting hemangiomas (127.2 +/- 6.3 and 122.5 +/- 6.3; P = 0.004).

CONCLUSIONS

GR and GRalpha are strongly expressed in hemangiomas and vascular malformations. The expression of GRalpha is closely related to the phase of the hemangioma. Determination of GR and GRalpha may be a positive significance to understand the information of hemangiomas and vascular malformations and may further help determining proper strategies of steroid therapy for hemangiomas and vascular malformations.

背景

血管瘤是儿童最常见的肿瘤。一些血管瘤可能因其位置、大小、行为或重要并发症的可能性而需要干预。糖皮质激素的药物治疗是主要治疗方法，但在治疗方案或候选药物选择上尚无共识，治疗效果各异，糖皮质激素有益作用的介导机制仍不清楚。本研究旨在调查糖皮质激素受体（GR）及其α异构体（GRα）在皮肤血管瘤和血管畸形中的表达模式。

方法

采用SP免疫组织化学技术检测80份标本中血管内皮细胞上GR（e-20）（GR）和GR（p-20）（GRα）的表达，这些标本包括33例增殖期血管瘤、32例消退期血管瘤、7例血管畸形以及8例正常皮肤组织，均取自婴幼儿。使用自动计算机辅助显微镜分析检测制备组织切片中的GR和GRα表达。比较不同肿瘤类型的平均灰度值。

结果

血管瘤和血管畸形中GR的平均灰度值分别为127.0±6.4和121.4±6.6，但差异无统计学意义（P = 0.104）。然而，这些值均明显高于正常皮肤，正常皮肤仅为108.6±6.8（与血管瘤和血管畸形比较，P分别为0.001和0.000）。增殖期和消退期血管瘤中GR的灰度分别为127.9±4.8和126.0±5.8，但差异不显著（P = 0.146）。然而，血管瘤、血管畸形和正常皮肤中GRα的表达呈逐步下降趋势（分别为127.3±5.4、120.4±6.1和109.9±5.3；P < 0.001）。增殖期血管瘤中GRα的表达高于消退期血管瘤（127.2±6.3和122.5±6.3；P = 0.004）。