Timotheadou Eleni, Skarlos Dimosthenis-Vasilios, Samantas Epaminondas, Papadopoulos Savvas, Murray Sam, Skrickova Jana, Christodoulou Christos, Papakostantinou Christos, Pectasides Dimitrios, Papakostas Pavlos, Kaplanova Jana, Vrettou Eleni, Karina Maria, Kosmidis Paraskevas, Fountzilas George
Department of Medical Oncology, Papageorgiou General Hospital, Aristotle University of Thessaloniki School of Medicine, Greece.
Anticancer Res. 2007 Nov-Dec;27(6C):4481-9.
Non-small cell lung cancer (NSCLC) remains a highly lethal disease worldwide and research for more effective treatment strategies is ongoing. Identification of molecular prognostic and predictive markers remains under investigation with results that are often conflicting.
Seventy-three patients (n= 73) with stage IB-IIIA completely resected NSCLC who were postoperatively treated with 6 cycles of paclitaxel and carboplatin from July 1998 to September 2002 took part in this study. Most stage IIIA patients subsequently received adjuvant radiotherapy. Cyclooxygenase-2 (COX-2), vascular endorhelial growth factor (VEGF), dihydrodiol dehydrogenase (DDH), receptor-binding cancer antigen expressed on SiSo cells (RCAS-1) and epidermic growth factor receptor (EGFR/HER-1) expression were assessed immunohistochemically; Heregulin family (HER1-4), VEGF and p53 were analysed by RT-PCR.
Totally, 61 (84%) men and 12 (16%) women with median age of 63 years and median PS of 0 were included in the study. There were 18 stage IB, 29 stage II and 26 stage IIIA patients. Sixty-seven samples were available for immunohistohemistry. COX-2 expression was detected in 24 patients (36%), VEGF in 14 (21%), RCAS1 in 31 (46%), DDH in 15 (22%). For EGFR, only 58 samples were evaluated, 13 of which were positive (22%). Messenger RNA expression data was only available for 60 patients; VEGF was detected in 32 (53%), p53 in 30 (50%), EGFR in 35 (58%), HER2 in 4 (7%) and HER3 in 19 (32%). HER4 was not detected in any sample. In the Cox analysis for overall survival (OS) and disease-free survival (DFS), none of the factors evaluated by IHC or RT-PCR reached statistical significance.
Even though the biomarkers tested are expressed in a significant proportion of lung tumors, none of them was found to be of prognostic significance in patients with NSCLC.
非小细胞肺癌（NSCLC）在全球范围内仍然是一种高致死性疾病，对更有效治疗策略的研究正在进行中。分子预后和预测标志物的鉴定仍在研究中，结果往往相互矛盾。
1998年7月至2002年9月期间，73例IB-IIIA期完全切除的NSCLC患者术后接受了6个周期的紫杉醇和卡铂治疗，并参与了本研究。大多数IIIA期患者随后接受了辅助放疗。采用免疫组织化学方法评估环氧合酶-2（COX-2）、血管内皮生长因子（VEGF）、二氢二醇脱氢酶（DDH）、SiSo细胞上表达的受体结合癌抗原（RCAS-1）和表皮生长因子受体（EGFR/HER-1）的表达；通过逆转录聚合酶链反应（RT-PCR）分析Heregulin家族（HER1-4）、VEGF和p53。
本研究共纳入61例（84%）男性和12例（16%）女性，中位年龄63岁，中位体能状态（PS）为0。其中IB期18例，II期29例，IIIA期26例。67份样本可用于免疫组织化学检测。24例（36%）患者检测到COX-2表达，14例（21%）检测到VEGF表达，31例（46%）检测到RCAS1表达，15例（22%）检测到DDH表达。对于EGFR，仅评估了58份样本，其中13份阳性（22%）。信使核糖核酸（mRNA）表达数据仅获得60例患者的；32例（53%）检测到VEGF，30例（50%）检测到p53，35例（58%）检测到EGFR，4例（7%）检测到HER2，19例（32%）检测到HER3。任何样本中均未检测到HER4。在总生存（OS）和无病生存（DFS）的Cox分析中，免疫组织化学或RT-PCR评估的任何因素均未达到统计学意义。
尽管所检测的生物标志物在相当比例的肺肿瘤中表达，但在NSCLC患者中均未发现具有预后意义。
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