Reduced FEZ1/LZTS1 expression and outcome prediction
Reduced FEZ1/LZTS1 expression and outcome prediction
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DOI：
10.1158/0008-5472.can-04-3461
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发表时间：
2005-02-15
期刊：
影响因子：
11.2
通讯作者：
Sozzi, G
中科院分区：
文献类型：
--
作者：
Nonaka, D;Fabbri, A;Sozzi, G
在肺癌中经常观察到染色体缺失，这表明肿瘤抑制基因的失活在这种肿瘤的发展中起着重要作用。染色体 Sp22 周围的区域是这些缺失的常见且早期目标，因此已研究了候选基因的存在。位于 Sp22 的 FEZ1/LZTS1 基因在许多 8p 缺失的癌症中失活，包括前列腺癌、食道癌、胃癌、膀胱癌和乳腺癌，并且 Fez1 蛋白已被证明可以抑制癌细胞的生长并调节有丝分裂。为了阐明 FEZ1 在肺癌中的作用，我们通过免疫组织化学分析了 103 个原发性肺癌标本中的 FEZ1 表达，其中包括 98 个非小细胞肺癌（57 个腺癌、32 个鳞状细胞癌、7 个大细胞癌和 2 个其他癌）和 5 个小细胞癌。 27 例 (26%) 观察到 Fez1 蛋白表达缺失，另外 43 例 (42%) 表现出免疫反应性大幅降低。 FEZ1 表达缺失与肿瘤分级之间存在正相关（P = 0.0345），并且 FEZ1 表达强的受试者死亡率有降低的趋势。总的来说，这些数据表明 FEZ1 在肺癌中的重要作用，并表明它有可能作为一种新的预后指标。
Chromosomal deletions are often observed in lung cancers suggesting that inactivation of tumor suppressor genes plays an important role in the development of this neoplasm. The region around chromosome Sp22 is a frequent and early target of these deletions and has therefore been investigated for the presence of candidate genes. The FEZ1/LZTS1 gene, located at Sp22, is inactivated in many cancers with 8p deletions, including prostate, esophageal, gastric, bladder, and breast cancer and the Fez1 protein has been shown to suppress growth of cancer cells and to regulate mitosis. To elucidate the role of FEZ1 in lung cancer, we have analyzed its expression by immunohistochemistry in 103 primary lung cancer specimens including 98 non-small cell lung cancers (57 adenocarcinomas, 32 squamous cell carcinomas, 7 large cell carcinomas, and 2 others) and five small cell carcinomas. Absence of Fez1 protein expression was observed in 27 cases (26%) and additional 43 cases (42%) showed strong reduction in immunoreactivity. There was a positive association between loss of FEZ1 expression and tumor grading (P = 0.0345) and a tendency toward a reduction in the mortality rate in subjects with strong FEZ1 expression. Overall, these data indicate an important role for FEZ1 in lung cancer and suggest the possibility that it may serve as a novel prognostic indicator.