Prudkin Ludmila, Behrens Carmen, Liu Diane D, Zhou Xian, Ozburn Natalie C, Bekele B Nebiyou, Minna John D, Moran Cesar, Roth Jack A, Ji Lin, Wistuba Ignacio I
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4009, USA.
Clin Cancer Res. 2008 Jan 1;14(1):41-7. doi: 10.1158/1078-0432.CCR-07-1252.
FUS1, a novel tumor-suppressor gene located in the chromosome 3p21.3 region, may play an important role in lung cancer development. Currently, FUS1-expressing nanoparticles have been developed for treating patients with lung cancer. However, the expression of Fus1 protein has not been examined in a large series of lung cancers and their sequential preneoplastic lesions.
Using tissue microarrays, we examined Fus1 immunohistochemical expression in 281 non-small cell lung carcinoma (NSCLC) and 22 small cell lung carcinoma tissue specimens and correlated the findings with patients' clinicopathologic features. To investigate the expression of Fus1 in the early sequential pathogenesis of NSCLC, we studied Fus1 expression in 211 histologically normal and mildly abnormal bronchial epithelia, and 118 bronchial and alveolar preneoplastic lesions obtained from patients with lung cancer.
Loss and reduction of expression was detected in 82% of NSCLCs and 100% of small cell lung carcinomas. In NSCLCs, loss of Fus1 immunohistochemical expression was associated with significantly worse overall survival. Bronchial squamous metaplastic and dysplastic lesions expressed significantly lower levels of Fus1 compared with normal (P = 0.014 and 0.047, respectively) and hyperplastic (P = 0.013 and 0.028, respectively) epithelia.
Our findings show a high frequency of Fus1 protein loss and reduction of expression in lung cancer, and suggests that this reduction may play an important role in the early pathogenesis of lung squamous cell carcinoma. These findings support the concept that FUS1 gene and Fus1 protein abnormalities could be used to develop new strategies for molecular cancer therapy for a significant subset of lung tumors.
FUS1是一种位于3号染色体p21.3区域的新型肿瘤抑制基因，可能在肺癌发生发展中发挥重要作用。目前，已开发出表达FUS1的纳米颗粒用于治疗肺癌患者。然而，尚未在大量肺癌及其序贯性癌前病变中检测Fus1蛋白的表达。
我们使用组织芯片检测了281例非小细胞肺癌（NSCLC）和22例小细胞肺癌组织标本中Fus1的免疫组化表达，并将结果与患者的临床病理特征相关联。为了研究Fus1在NSCLC早期序贯发病机制中的表达，我们研究了211例组织学正常和轻度异常的支气管上皮以及118例从肺癌患者获得的支气管和肺泡癌前病变中Fus1的表达。
在82%的NSCLC和100%的小细胞肺癌中检测到表达缺失和降低。在NSCLC中，Fus1免疫组化表达缺失与总体生存率显著较差相关。与正常上皮（分别为P = 0.014和0.047）和增生上皮（分别为P = 0.013和0.028）相比，支气管鳞状化生和发育异常病变中Fus1表达水平显著降低。
我们的研究结果显示肺癌中Fus1蛋白缺失和表达降低的频率较高，并表明这种降低可能在肺鳞状细胞癌的早期发病机制中起重要作用。这些发现支持这样的概念，即FUS1基因和Fus1蛋白异常可用于为相当一部分肺肿瘤开发新的分子癌症治疗策略。
