Department of Oral and Maxillofacial Surgery and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, South Korea.
J Oral Pathol Med. 2010 May;39(5):368-75. doi: 10.1111/j.1600-0714.2009.00844.x. Epub 2009 Dec 29.
BACKGROUND: Poor prognosis of oral squamous cell carcinoma (OSCC) is partly attributed to the lack of significant tumor marker for accurate staging and prognostication. We have evaluated survivin, which is a member of the inhibitor of apoptosis family as a cancer marker associated with proliferation, angiogenesis, oral carcinogenesis, and OSCC patient survival, as we reported a prognostic significance of survivin expression in lymph node previously. METHODS: To evaluate survivin expression in six OSCC cell lines, Western blotting was performed. Hamster oral carcinogenesis model was used to observe changes of survivin expression in oral carcinogenesis. Finally, we assessed the diagnostic and prognostic significance of survivin in a series of 38 primary OSCC through immunohistochemistry (CD31, PCNA) and Kaplan-Meier's test. RESULTS: Survivin expression was detected in all OSCC cell lines at a varying level but not observed in normal gingival keratinocyte cells. In hamster model, survivin expression was observed from 8 weeks through 16 weeks and the intensity of expression became strong until 16 weeks. Clinicopathological analysis revealed a significant correlation between survivin expression and lymph node metastasis (P = 0.006) and proliferation (P < 0.001). However, there was no significant relationship with differentiation, micro vessel density, and cancer stage based on TNM. Survivin overexpression had a significant negative effect on survival of patients. CONCLUSIONS: These results demonstrate the significant relationship between survivin expression and oral carcinogenesis and aggressiveness of OSCC including survival rate of patient. Survivin therefore may be used as a significant cancer marker to gain prognostic information of OSCC.
背景:口腔鳞状细胞癌(OSCC)预后较差,部分原因是缺乏用于准确分期和预后的显著肿瘤标志物。我们评估了生存素,它是凋亡抑制因子家族的成员,作为与增殖、血管生成、口腔癌变和 OSCC 患者生存相关的癌症标志物,因为我们之前报道过生存素表达与淋巴结预后相关。
方法:通过 Western blot 检测 6 种 OSCC 细胞系中的生存素表达。使用仓鼠口腔癌变模型观察口腔癌变过程中生存素表达的变化。最后,我们通过免疫组织化学(CD31、PCNA)和 Kaplan-Meier 检验评估了 38 例原发性 OSCC 中生存素的诊断和预后意义。
结果:在所有 OSCC 细胞系中均检测到生存素表达,但在正常牙龈角质形成细胞中未观察到。在仓鼠模型中,从 8 周到 16 周观察到生存素表达,表达强度在 16 周时增强。临床病理分析显示,生存素表达与淋巴结转移(P=0.006)和增殖(P<0.001)显著相关。然而,根据 TNM,与分化、微血管密度和癌症分期无显著关系。生存素过表达对患者的生存有显著的负面影响。
结论:这些结果表明,生存素表达与口腔癌变和 OSCC 的侵袭性(包括患者的生存率)之间存在显著关系。因此,生存素可能被用作一个重要的癌症标志物,以获得 OSCC 的预后信息。
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