Expression of mesenchyme-specific gene HMGA2 in squamous cell carcinomas of the oral cavity
Expression of mesenchyme-specific gene HMGA2 in squamous cell carcinomas of the oral cavity
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DOI：
10.1158/0008-5472.can-03-1855
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发表时间：
2004-03-15
期刊：
影响因子：
11.2
通讯作者：
Imai, K
中科院分区：
文献类型：
--
作者：
Miyazawa, J;Mitoro, A;Imai, K
上皮来源的癌细胞在肿瘤的进展过程中倾向于获得成纤维细胞特征，即上皮-间质转化。HMGA2是一种结构转录因子，在未分化间质中表达并启动间质肿瘤的形成。然而，在上皮型癌病理表达的生物学后果是有争议的。本研究旨在探讨其在口腔鳞状细胞癌中的表达模式。通过常规逆转录- pcr检测，HMGA2仅在癌细胞系和组织中检测到，而在正常角质形成细胞和牙龈中检测不到。实时定量逆转录pcr显示，HMGA2在癌组织中的表达量是正常牙龈的160倍，在癌细胞系中的表达量是正常角质形成细胞的11倍。42例癌中，73.8%的癌组织表达HMGA2，且HMGA2仅局限于浸润前部，细胞呈上皮-间质转化。14例未发生淋巴结转移的患者HMGA2染色阳性，并复发。此外，23例肿瘤复发死亡患者的肿瘤中均有HMGA2染色，HMGA2染色与患者的长期生存相关（P < 0.01）。多因素危险因素分析显示HMGA2表达是疾病特异性总生存的独立预后价值（P < 0.01）。这些结果表明，HMGA2与癌的侵袭性有关，检测HMGA2的表达在口腔癌的临床治疗中是一种有用的预测和预后工具。
Carcinoma cells of epithelial origin are predisposed to acquire a fibroblastic feature during progression of neoplasm referred to as the epithelial-mesenchymal transition. HMGA2 is an architectural transcriptional factor that is expressed in the undifferentiated mesenchyme and initiates mesenchymal tumor formation. However, the biological consequence of the expression in the pathology of epithelial-type carcinomas is controversial. The present study was conducted to dissect the expression pattern in oral squamous cell carcinomas. HMGA2 was detected exclusively in carcinoma cell lines and tissues, but not in normal keratinocytes and gingival, by conventional reverse transcription-PCR. Quantitative real-time reverse transcription-PCR demonstrated 160-fold more HMGA2 expression in carcinoma tissues than in normal gingiva and 11-fold more HMGA2 expression in carcinoma cell lines than in normal keratinocytes. HMGA2 expression was observed by immunohistochemistry in 73.8% of 42 carcinomas and localized to the invasive front, where the cells exhibi It the epithelial-mesenchymal transition. Fourteen patients who had been classified into a group without lymph node metastasis were positive for HMGA2 staining, and the disease recurred. Furthermore, carcinomas from all 23 patients who died of tumor recurrence stained for HMGA2, and HMGA2 staining was correlated to long-term survival of patients (P < 0.01). Multivariate risk factor analysis demonstrated that HMGA2 expression was an independent prognostic value for disease-specific overall survival (P < 0.01). These results suggest that HMGA2 contributes to the aggressiveness of carcinoma and that detection of HMGA2 expression is a useful predictive and prognostic tool in clinical management of oral carcinomas.