Choe Ji-Young, Yun Ji Yun, Jeon Yoon Kyung, Kim Se Hoon, Choung Ho-Kyung, Oh Sohee, Park Mira, Kim Ji Eun
Department of Pathology, Seoul National University, College of Medicine, Seoul, Korea Department of Pathology, Seoul National University Bundang Hospital, Gyeonggi-Do, Korea.
Department of Pathology, Seoul National University, College of Medicine, Seoul, Korea Department of Pathology, Seoul National University Hospital, Seoul, Korea.
J Clin Pathol. 2015 Jan;68(1):6-11. doi: 10.1136/jclinpath-2014-202434. Epub 2014 Oct 8.
This study aimed to examine the expression of Sonic hedgehog (SHH) signalling proteins in retinoblastoma and to evaluate its clinical significance.
Seventy-nine enucleated retinoblastoma tumours were investigated immunohistochemically using antibodies against SHH pathway proteins, such as SHH, glioma-associated oncogene homologue (GLI) 1, GLI2, GLI3 and ABC binding cassette G2 (ABCG2). Western blotting of SHH signalling proteins was performed in two retinoblastoma cell lines.
SHH was expressed in most retinoblastoma cases (78 of 79, 98.7%), with 21 cases (26.6%) showing strong expression. GLI1 and GLI2 were also frequently expressed: 67 of 78 cases (85.9%) and 71 of 77 cases (92.2%), respectively. GLI3, a transcriptional repressor, was expressed at low levels in 23 of the 78 cases (29.5%). High ABCG2 expression was found in 23 of the 78 cases (29.5%). High expression levels of these proteins in retinoblastoma cell lines were confirmed by western blotting. The expression of SHH was associated with advanced stages, local invasion and metastasis (all p<0.05).
SHH signalling molecules were frequently expressed in retinoblastoma tumour cells, and high SHH expression was closely related to an advanced disease status. Our results suggest that the SHH signalling pathway may play a role in the progression of retinoblastoma.
本研究旨在检测视网膜母细胞瘤中 Sonic hedgehog（SHH）信号蛋白的表达，并评估其临床意义。
使用针对 SHH 通路蛋白（如 SHH、胶质瘤相关癌基因同源物（GLI）1、GLI2、GLI3 和 ABC 转运蛋白 G2（ABCG2））的抗体，对 79 个摘除的视网膜母细胞瘤肿瘤进行免疫组织化学研究。在两种视网膜母细胞瘤细胞系中进行 SHH 信号蛋白的 Western 印迹分析。
大多数视网膜母细胞瘤病例（79 例中的 78 例，98.7%）表达 SHH，其中 21 例（26.6%）呈强表达。GLI1 和 GLI2 也经常表达，分别为 78 例中的 67 例（85.9%）和 77 例中的 71 例（92.2%）。转录抑制因子 GLI3 在 78 例中的 23 例（29.5%）中低水平表达。78 例中的 23 例（29.5%）发现 ABCG2 高表达。Western 印迹证实了这些蛋白在视网膜母细胞瘤细胞系中的高表达水平。SHH 的表达与晚期、局部侵袭和转移相关（所有 p<0.05）。
SHH 信号分子在视网膜母细胞瘤肿瘤细胞中频繁表达，高 SHH 表达与疾病晚期密切相关。我们的结果表明，SHH 信号通路可能在视网膜母细胞瘤的进展中起作用。
