Segawa Emi, Sakurai Kazunari, Kishimoto Hiromitsu, Takaoka Kazuki, Noguchi Kazuma, Hashitani Susumu, Hirota Seiichi, Urade Masahiro
Department of Oral and Maxillofacial Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, Japan.
Oral Oncol. 2008 Jul;44(7):664-71. doi: 10.1016/j.oraloncology.2007.08.014. Epub 2007 Nov 9.
The involvement of cyclooxygenase (COX)-2 in oral carcinogenesis and outcome of the patients is not fully understood. To determine whether COX-2 expression could serve as an indicator for them, we examined the expression of COX-2 and DNA topoisomerase (DNA-Topo) II alpha as an index of cell proliferating activity in precancerous and cancerous lesions of the oral mucosa. A 164 samples composed of 60 intraepithelial dysplasias (IEDs), 12 carcinomas in situ (CISs), 72 squamous cell carcinomas (SCCs) including 12 early invasive SCCs, 10 undifferentiated carcinomas (UCs), and 10 epithelial hyperplasias (EHPs) in the oral mucosa were examined immunohistochemically for COX-2 and DNA-Topo II alpha. Normal squamous epithelium as the control showed no COX-2 expression, whereas 41% of IEDs, 67% of CISs, 74% of SCCs, and 86% of UCs demonstrated increased COX-2 expression with elevated DNA-Topo II alpha labeling index (LI). High COX-2 expression was also observed in 61% of EHPs, but DNA-Topo II alpha LI was very low. Increased expression of COX-2 protein correlated with elevated DNA-Topo II alpha LI, indicating that COX-2 may contribute to malignant transformation and tumor growth. These two enzyme activities were increased as T, N, and M categories and stages proceeded. The patients with high expression of both COX-2 and DNA-Topo II alpha showed poor prognosis. Our results suggested that COX-2 expression become a possible indicator in oral carcinogenesis and may reflect the outcome of the patients.
环氧化酶（COX）-2在口腔癌发生及患者预后中的作用尚未完全明确。为确定COX-2表达是否可作为其指标，我们检测了COX-2及DNA拓扑异构酶（DNA-Topo）IIα的表达，后者作为口腔黏膜癌前病变和癌性病变中细胞增殖活性的指标。对164份样本进行免疫组化检测，样本包括60例上皮内发育异常（IED）、12例原位癌（CIS）、72例鳞状细胞癌（SCC）（其中包括12例早期浸润性SCC）、10例未分化癌（UC）以及10例口腔黏膜上皮增生（EHP），检测指标为COX-2和DNA-Topo IIα。作为对照的正常鳞状上皮未显示COX-2表达，而41%的IED、67%的CIS、74%的SCC以及86%的UC显示COX-2表达增加，且DNA-Topo IIα标记指数（LI）升高。61%的EHP也观察到COX-2高表达，但DNA-Topo IIα LI非常低。COX-2蛋白表达增加与DNA-Topo IIα LI升高相关，表明COX-2可能促成恶性转化和肿瘤生长。随着T、N和M分类及分期进展，这两种酶活性增加。COX-2和DNA-Topo IIα均高表达的患者预后较差。我们的结果提示，COX-2表达可能成为口腔癌发生的一个指标，并可能反映患者的预后。
