WWOX expression in different histologic types and subtypes of non-small cell lung cancer
WWOX expression in different histologic types and subtypes of non-small cell lung cancer
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DOI：
10.1158/1078-0432.ccr-06-2016
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发表时间：
2007-02-01
影响因子：
11.5
通讯作者：
Aqeilan, Rami Ishaq
中科院分区：
文献类型：
--
作者：
Donati, Valentina;Fontanini, Gabriella;Aqeilan, Rami Ishaq
目的：非小细胞肺癌（Non-small cell lung cancer，NSCLC）的组织病理学分型和临床表现具有异质性，生存率极低。WWOX（含WW结构域的氧化还原酶）是一种肿瘤抑制基因，其表达在几种癌症中发生改变。本研究的目的是通过确定WWOX的发病和预后意义，更好地确定WWOX在NSCLC肿瘤发生和进展中的作用。采用免疫组化方法检测170例NSCLC患者中WWOX蛋白的表达（101例鳞状细胞癌，66例腺癌，3例大细胞癌），并与组织病理学相关（组织型、亚型、分级、肿瘤淋巴结转移、分期、细胞增殖指数Ki 67/MIB 1）和临床（年龄、性别、局部复发、远处转移、总生存率和无病生存率）特征。WWOX在84.9%的NSCLC中表达缺失/减少，而在80.5%的邻近正常肺组织中表达正常。WWOX表达与肿瘤组织学（P = 1.1 x 10（-5））和组织学分级（P = 0.0081）密切相关：鳞状细胞癌和低分化肿瘤中WWOX表达缺失/强烈降低的病例百分比较高。关于腺癌，细支气管肺泡型在62.5%的病例中显示正常WWOX表达，而在实性和腺泡型中，观察到WWOX表达缺失/非常低的病例的患病率（分别为79.2%和50%）。结论：WWOX表达缺失在不同组织型和亚型NSCLC的发生中起不同作用，并与肿瘤的高侵袭性（G（3）;高增殖活性）有关。
Purpose: Non-small cell lung cancer (NSCLC) has heterogeneous histopathologic classification and clinical behavior and very low survival rate. WWOX (WW domain-containing oxicloreductase) is a tumor suppressor gene, and its expression is altered in several cancers. The purpose of this study is to better define the role of WWOX in NSCLC tumorigenesis and progression by determining its pathogenetic and prognostic significance.Experimental Design: WWOX protein expression was evaluated by immunohistochemistry in 170 patients with NSCLC (101 squamous cell carcinomas, 66 adenocarcinomas, 3 large cell carcinomas) and was correlated with histopathologic (histotype, subtype, grade, tumor-node-metastasis, stage, index of cell proliferation Ki67/MIB1) and clinical (age, gender, local recurrences, distant metastases, overall survival, and disease-free survival) characteristics.Results: WWOX expression was absent/reduced in 84.9% of NSCLCs, whereas it was normal in 80.5% of adjacent normal lung tissues. WWOX expression was strongly associated with tumor histology (P = 1.1 x 10(-5)) and histologic grade (P = 0.0081): the percentage of cases with absent/strongly reduced WWOX expression was higher in squamous cell carcinomas and in poorly differentiated tumors. Regarding adenocarcinoma, bronchioloalveolar pattern showed normal WWOX expression in 62.5% of the cases, whereas in solid and acinar patterns, a prevalence of cases with absent/very low WWOX expression was observed (79.2% and 50%, respectively). Finally, weak WWOX staining intensity was related to the high index of cell proliferation (P = 0.0012).Conclusions: Our results suggest that the loss of WWOX expression plays different roles in tumorigenesis of distinct histotypes and subtypes of NSCLC and is related to high aggressiveness (G(3); high proliferating activity) of tumors.