Medical Oncology Unit Department of Medicine, College of Medicine, Sultan Qaboos University, PO Box 35, 123Muscat, Oman.
Med Oncol. 2012 Sep;29(3):1739-47. doi: 10.1007/s12032-011-0098-3. Epub 2011 Nov 3.
Gastric cancer remains a significant global health burden with poor treatment outcome. New treatment modalities that target inflammation, proliferation, and angiogenesis have been used in various cancers, including gastric cancer. We sought to study the pattern of expression of two important proteins, cyclooxygenase-2 and epidermal growth factor receptor, and their association with microvascular density, clinicopathological features, and survival in Arab Omani patients with gastric cancer. Formalin-fixed, paraffin-embedded tumors were studied by immunohistochemistry using monoclonal antibodies to cyclooxygenase-2, epidermal growth factor receptor, and CD34. The immunohistochemical results were correlated with clinicopathological features and survival. In our study population, we found a male/female ratio of 72:43, a median age of 59 years, stage III and IV incidence of 66.9%, and a median follow-up of 96 months. Positive expression rates of cyclooxygenase-2 and epidermal growth factor receptor were 89.6 and 23.5%, respectively. The median microvascular density value was 52.5. When this value was determined as the cut-off point, 50% of patients were found to have high microvascular density. Epidermal growth factor receptor over-expression correlated with high microvascular density values, advanced lymph node involvement (N3), and TNM stage presentation (III and IV). Similarly, lymph node involvement was associated with cyclooxygenase-2 over-expression and high microvascular density. Univariate analysis showed that epidermal growth factor receptor over-expression, pathological T3 and T4 disease, and overall stage III and IV disease were adverse prognostic factors. On multivariate analysis using a Cox regression model, expression of epidermal growth factor receptor, and advanced TNM stage were significant adverse prognostic factors for overall survival. Expression of epidermal growth factor receptor in Arab Omani patients with gastric cancer correlates with aggressive tumor characteristics and is an independent prognostic factor. Further clinical studies are needed to evaluate the utility of epidermal growth factor receptor immunohistochemistry as a tool for gastric cancer treatment.
胃癌仍然是一个严重的全球健康负担，治疗效果不佳。针对炎症、增殖和血管生成的新治疗方法已在各种癌症中得到应用，包括胃癌。我们试图研究两种重要蛋白质，环氧化酶-2 和表皮生长因子受体，在阿拉伯阿曼胃癌患者中的表达模式及其与微血管密度、临床病理特征和生存的关系。使用针对环氧化酶-2、表皮生长因子受体和 CD34 的单克隆抗体，通过免疫组织化学对福尔马林固定、石蜡包埋的肿瘤进行研究。将免疫组织化学结果与临床病理特征和生存相关联。在我们的研究人群中，我们发现男女比例为 72:43，中位年龄为 59 岁，III 期和 IV 期的发生率为 66.9%，中位随访时间为 96 个月。环氧化酶-2 和表皮生长因子受体的阳性表达率分别为 89.6%和 23.5%。微血管密度值的中位数为 52.5。当将此值确定为截止点时，发现 50%的患者具有高微血管密度。表皮生长因子受体的过度表达与高微血管密度值、淋巴结受累（N3）和 TNM 分期呈阳性相关。同样，淋巴结受累与环氧化酶-2 过表达和高微血管密度相关。单因素分析显示，表皮生长因子受体过度表达、病理 T3 和 T4 疾病以及总 III 和 IV 期疾病是不良预后因素。使用 Cox 回归模型进行多因素分析显示，表皮生长因子受体表达和晚期 TNM 分期是总生存的独立不良预后因素。阿拉伯阿曼胃癌患者表皮生长因子受体的表达与侵袭性肿瘤特征相关，是独立的预后因素。需要进一步的临床研究来评估表皮生长因子受体免疫组织化学作为胃癌治疗工具的效用。
