HIPK2 Overexpression and Its Prognostic Role in Human Papillomavirus-Positive Tonsillar Squamous Cell Carcinoma.
HIPK2 Overexpression and Its Prognostic Role in Human Papillomavirus-Positive Tonsillar Squamous Cell Carcinoma.
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DOI：
10.1155/2017/1056427
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发表时间：
2017
影响因子：
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通讯作者：
Rho YS
中科院分区：
文献类型：
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作者：
Kwon MJ;Kang SY;Nam ES;Cho SJ;Rho YS
扁桃体鳞状细胞癌(TSCCs)是最常见的人类乳头瘤病毒(HPV)相关性口咽癌，预后不良。同源域相互作用蛋白激酶2(HIPK2)是P53的中心调节因子，在DNA损伤反应中参与细胞凋亡。HIPK2通过与HPVE6结合，参与HPV相关的子宫颈和皮肤癌的发生，从而阻止细胞凋亡，促进肿瘤进展。然而，其在TSCC中的临床和预后意义仍不清楚。采用实时荧光定量逆转录聚合酶链式反应技术检测20例正常扁桃体和20例舌鳞癌组织中HIPK2基因的表达水平。对79例手术切除标本进行HIPK2免疫组织化学染色。HIPK2在57%的TSCC中表达，且HIPK2蛋白表达和HIPK2mRNA水平在TSCC中高于正常扁桃体。HIPK2的过度表达与低分化癌和低酒精摄入量有关，是影响TSCC患者总体生存和无病生存(DFS)的独立预后因素，而对于接受术后放疗的患者的DFS则是阴性的独立预后因素。HIPK2过表达与HPV阳性TSCC中较差的DFS显著相关，而在HPV阴性肿瘤中则不显著。HIPK2过表达可能是预测预后和复发风险的潜在预后指标，尤其是在HPV阳性的TSCC患者中。
Tonsillar squamous cell carcinomas (TSCCs) are the most common human papillomavirus- (HPV-) associated oropharyngeal cancers with poor prognosis. Homeodomain-interacting protein kinase 2 (HIPK2) is a central regulator of p53, which participates in apoptosis during the DNA damage response. HIPK2 is involved in HPV-associated uterine cervical and cutaneous carcinogenesis through its binding of HPV E6, thereby preventing apoptosis and contributing to tumor progression. However, its clinical and prognostic significance in TSCC remains unclear. HIPK2 mRNA levels were analyzed in 20 normal tonsils and 20 TSCC specimens using real-time reverse transcription polymerase chain reaction. Immunohistochemistry of HIPK2 was performed in 79 resected specimens. HIPK2 was expressed in 57% of the TSCCs, and HIPK2 protein expression and HIPK2 mRNA levels were higher in TSCCs than in normal tonsils. HIPK2 overexpression was associated with poorly differentiated carcinoma and low alcohol consumption and was an independent prognostic factor for overall survival and disease-free survival (DFS) in TSCC and a negative independent prognostic factor for DFS in patients receiving postoperative radiotherapy. HIPK2 overexpression had a significant association with poorer DFS in HPV-positive TSCCs, but not in HPV-negative tumors. HIPK2 overexpression may be a potential prognostic marker for predicting prognoses and a high risk of recurrence, particularly in patients with HPV-positive TSCC.