Expression of Sonic Hedgehog Signaling Pathway Related Proteins in Retinoblastoma
Ji-Young Choe, Ji Yun Yun, Yoon Kyung Jeon, Se Hoon Kim, Ji Eun Kim. Seoul National Univeristy Hospital, Seoul, Korea; Seoul National University Boramae Hospital, Seoul, Korea; Yonsei University Hospital, Seoul, Korea
Background: Sonic hedgehog (SHH) protein is a member of secreted signaling molecules that is involved in early embryonic development of various organs. Dysregulation of this pathway has been reported in several cancers but not yet assessed in retinoblastoma.
Design: Fifty-four cases of retinoblastoma were investigated immunohistochemically using antibodies against SHH pathway proteins such as SHH, GLI1, GLI2, GLI3, and ABC binding cassette G2 (ABCG2) on tissue microarray blocks. Western blot (WB) analysis was performed to confirm the expression of SHH and GLI proteins in two retinoblastoma cell lines, Y-79 and WERI-Rb-1. Correlation between the expression of SHH signaling proteins and various clinicopathologic parameters was statistically analyzed.
Results: SHH was expressed in most cases of retinoblastoma (52 of 54, 96.3%), 10 cases (18.5%) showing strong expression. GLI1 and GLI2 were also highly expressed, 44 of 54 cases (81.5%) and 49 of 53 cases (92.5%), respectively. GLI3, a transcriptional repressor, was expressed in 23 of 54 cases (42.6%) at low levels. ABCG2 expression was found in 12 of 54 cases (22.2%). High expression levels of these proteins in retinoblastoma cell lines were confirmed by WB. Expression of SHH correlated with advanced T stage (p=0.026), optic nerve invasion (p=0.014), necrosis (p=0.036) and distant metastasis (p =0.029). Expression of ABCG2, which represents chemoresistance, positively correlated with that of SHH (p=0.002).
Conclusions: SHH related proteins are highly expressed in retinoblastoma tumor cells. SHH expression is closely related to advanced disease and overexpression of chemoresistance protein, ABCG2. These findings strongly suggest that SHH signaling pathway may play a significant role in progression of retinoblastoma.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 310, Wednesday Afternoon