Siironen Päivi, Ristimäki Ari, Narko Kirsi, Nordling Stig, Louhimo Johanna, Andersson Sture, Haapiainen Reijo, Haglund Caj
Department of Surgery, Helsinki University Central Hospital, P O Box 340, FIN-00029 HUCH, Helsinki, Finland.
Endocr Relat Cancer. 2006 Jun;13(2):465-73. doi: 10.1677/erc.1.01114.
In papillary thyroid cancer (PTC), age appears to be the most important single prognostic factor. Another characteristic feature is the lack of association between survival and lymph node metastases. Earlier, we found that expression of cyclooxygenase-2 (COX-2) is higher in older PTC patients, in agreement with the finding that older patients have a worse prognosis. Recent findings suggest that COX-2 can up-regulate vascular endothelial growth factor-C (VEGF-C) expression. Here, we investigated whether expression of VEGF-C differs between young and older PTC patients and whether expression of VEGF-C and COX-2 are correlated. Our retrospective study comprised 106 PTC patients selected by age: those under 35 or over 55 at diagnosis. Paraffin-embedded tissue samples were analysed by immunohistochemistry for VEGF-C protein expression. Furthermore, we investigated by quantitative RT-PCR and enzyme immunoassay the relationship between VEGF-C and COX-2 expression in papillary thyroid cancer cells (NPA cells). VEGF-C expression was significantly increased with age. In the tumours from older lymph node-positive (N1) patients, VEGF-C expression was significantly higher than in the tumours from young N1 patients. Moreover, all patients who died of cancer or who developed distant metastases were old, and most tumours from these patients (4 of 5) expressed VEGF-C and had had nodal metastases at the time of primary operation. Immunohistochemically, expression of COX-2 and VEGF-C correlated strongly. In cell culture, this correlation was not so clear, because the COX-2 selective inhibitor, NS-398, did not reduce VEGF-C expression. However, as both COX-2 and VEGF-C were induced by the tumour promoter phorbol 12-myristate 13-acetate (PMA), the same factors may control them both.
在甲状腺乳头状癌（PTC）中，年龄似乎是最重要的单一预后因素。另一个特征是生存率与淋巴结转移之间缺乏关联。早些时候，我们发现环氧合酶-2（COX-2）在老年PTC患者中的表达较高，这与老年患者预后较差的发现一致。最近的研究结果表明，COX-2可上调血管内皮生长因子-C（VEGF-C）的表达。在此，我们研究了年轻和老年PTC患者之间VEGF-C的表达是否存在差异，以及VEGF-C和COX-2的表达是否相关。我们的回顾性研究纳入了106例按年龄选择的PTC患者：诊断时年龄在35岁以下或55岁以上。通过免疫组织化学分析石蜡包埋组织样本中VEGF-C蛋白的表达。此外，我们通过定量逆转录-聚合酶链反应（RT-PCR）和酶免疫测定法研究了甲状腺乳头状癌细胞（NPA细胞）中VEGF-C和COX-2表达之间的关系。VEGF-C的表达随年龄显著增加。在老年淋巴结阳性（N1）患者的肿瘤中，VEGF-C的表达明显高于年轻N1患者的肿瘤。此外，所有死于癌症或发生远处转移的患者均为老年患者，这些患者中的大多数肿瘤（5例中的4例）表达VEGF-C，并且在初次手术时已有淋巴结转移。免疫组织化学显示，COX-2和VEGF-C的表达密切相关。在细胞培养中，这种相关性并不明显，因为COX-2选择性抑制剂NS-398并未降低VEGF-C的表达。然而，由于COX-2和VEGF-C均由肿瘤启动子佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）诱导，可能有相同的因素控制它们两者。
