拓扑异构酶IIα蛋白在涎腺癌中的差异表达：组织发生学及预后意义
Differential expression of topoisomerase IIalpha protein in salivary gland carcinomas: histogenetic and prognostic implications.
作者信息
Maruya Shin-ichiro, Shirasaki Takashi, Nagaki Takahiko, Kakehata Seiji, Kurotaki Hidekachi, Mizukami Hiroki, Shinkawa Hideichi
机构信息
Department of Otolaryngology, Hirosaki University School of Medicine, Hirosaki, Japan.
出版信息
BMC Cancer. 2009 Feb 27;9:72. doi: 10.1186/1471-2407-9-72.
BACKGROUND
Salivary gland carcinomas are relatively uncommon heterogeneous malignancies characterized by locoregional invasion and distant metastasis. Topoisomerase IIalpha (topoIIalpha), located at chromosome 17q21-22, is considered a major mediator of cell proliferation and DNA replication. The purpose of this study was to evaluate the expression of topoIIalpha in various types of salivary gland tumors and its biological significance.
METHODS
The protein expression of topoIIalpha was evaluated immunohistochemically in formalin-fixed, paraffin-embedded tissue from 54 salivary gland carcinomas and 20 benign tumors (10 pleomorphic adenomas and 10 Warthin's tumors). The primary salivary gland carcinoma specimens consisted of 17 adenoid cystic carcinomas, 7 adenocarcinomas not otherwise specified, 7 mucoepidermoid carcinomas, 6 salivary duct carcinomas, 3 acinic cell carcinomas, 3 carcinomas ex pleomorphic adenomas, 3 epithelial-myoepithelial carcinomas, 2 carcinosarcomas, 2 lymphoepithelial carcinomas, 2 myoepithelial carcinomas, 1 oncocytic carcinoma, and 1 squamous cell carcinoma. The associations between clinicopathological factors and outcome were analyzed.
RESULTS
Of the 54 primary salivary gland carcinomas, 38 (70%) showed positive expression (> or = 10%) of topoIIalpha protein, and 16 carcinomas (30%) and all benign tumors were negative (p < 0.001). Expression of topoIIalpha was more frequently observed in salivary duct carcinoma, carcinoma ex pleomorphic adenoma, adenocarcinoma, and adenoid cystic carcinoma, solid type, and it was associated with advanced stage and shortened survival.
CONCLUSION
The results of the present study suggest that topoIIalpha expression is associated with histologically aggressive subtypes and shortened survival. Furthermore, it may provide useful prognostic information and suggests the potential efficacy of topoIIalpha-targeting therapy in patients with salivary gland carcinoma.
背景
涎腺癌是相对少见的异质性恶性肿瘤，其特征为局部区域侵犯和远处转移。位于17号染色体q21 - 22的拓扑异构酶IIα（topoIIα）被认为是细胞增殖和DNA复制的主要调节因子。本研究的目的是评估topoIIα在各种涎腺肿瘤中的表达及其生物学意义。
方法
采用免疫组织化学方法评估topoIIα在54例涎腺癌和20例良性肿瘤（10例多形性腺瘤和10例沃辛瘤）的福尔马林固定、石蜡包埋组织中的蛋白表达。原发性涎腺癌标本包括17例腺样囊性癌、7例未另行规定的腺癌、7例黏液表皮样癌、6例涎腺导管癌、3例腺泡细胞癌、3例多形性腺瘤恶变、3例上皮 - 肌上皮癌、2例癌肉瘤、2例淋巴上皮癌、2例肌上皮癌、1例嗜酸性细胞癌和1例鳞状细胞癌。分析临床病理因素与预后的相关性。
结果
在54例原发性涎腺癌中，38例（70%）显示topoIIα蛋白阳性表达（≥10%），16例癌（30%）和所有良性肿瘤均为阴性（p < 0.001）。topoIIα表达在涎腺导管癌、多形性腺瘤恶变、腺癌和腺样囊性癌实体型中更常见，且与晚期和生存期缩短相关。
结论
本研究结果表明，topoIIα表达与组织学上侵袭性亚型及生存期缩短相关。此外，它可能提供有用的预后信息，并提示topoIIα靶向治疗对涎腺癌患者的潜在疗效。
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