胶质1
淋巴瘤
癌症研究
弥漫性大B细胞淋巴瘤
胶质2
慢性淋巴细胞白血病
滤泡性淋巴瘤
Abcg2型
刺猬
音猬因子
胶质3
刺猬信号通路
病理
生物
BCL10
平滑
白血病
医学
信号转导
免疫学
基因表达
ATP结合盒运输机
细胞生物学
基因
遗传学
运输机
抑制因子
作者
Ji Eun Kim,Rajesh Singh,Jeong Hee Cho‐Vega,Ηλίας Δράκος,Yogesh Davuluri,Faisal A Khokhar,Luis Fayad,L. Jeffrey Medeiros,Francisco Vega
出处
期刊:Modern Pathology
[Springer Nature]
日期:2009-10-01
卷期号:22 (10): 1312-1320
被引量:88
标识
DOI:10.1038/modpathol.2009.98
摘要
Dysregulation of the sonic hedgehog (SHH) signaling pathway has been shown in several cancer types, but has not been explored in diffuse large B-cell lymphoma. We assessed 67 cases of diffuse large B-cell lymphoma for expression of SHH (ligand), GLI1, GLI2 and GLI3 (transcriptional effectors of SHH signaling), and the ATP-binding cassette (ABC)G2 (a downstream target of SHH signaling), using immunohistochemistry. For comparison, we assessed the expression levels of these proteins in 28 cases of follicular lymphoma, 5 chronic lymphocytic leukemia/small lymphocytic lymphoma, and 5 reactive lymph nodes. In diffuse large B-cell lymphoma, SHH was expressed in 61 of 67 (91%) cases, GLI1 in 62 of 67 (93%), GLI2 in 41 of 56 (73%), and GLI3 in 22 of 56 (39%). Expression of ABCG2 was detected in 52 of 55 (95%) cases and was high in 15 (27%) cases. SHH expression positively correlated with expression levels of ABCG2 (P=0.05). Patients with diffuse large B-cell lymphoma with high ABCG2 expression showed significantly shorter overall survival (P=0.031) and failure-free survival (P=0.029) compared with patients with tumors with low or no expression of ABCG2. Diffuse large B-cell lymphomas expressed SHH, and GLI1, GLI2, and GLI3 more frequently and more intensely than cases of follicular lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma. In conclusion, our data show that SHH signaling proteins and ABCG2 are aberrantly expressed in diffuse large B-cell lymphoma and that ABCG2 expression has prognostic implications. These findings also provide evidence that dysregulation of the SHH pathway may be involved in the pathogenesis of diffuse large B-cell lymphoma.
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