Songun I, Litvinov S V, van de Velde C J H, Pals S T, Hermans J, van Krieken J H J M
Department of Surgery, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Br J Cancer. 2005 May 9;92(9):1767-72. doi: 10.1038/sj.bjc.6602519.
Preoperative staging of gastric cancer is difficult and not optimal. The TNM stage is an important prognostic factor, but it can only be assessed reliably after surgery. Therefore, there is need for additional, reliable prognostic factors that can be determined preoperatively in order to select patients who might benefit from (neo) adjuvant treatment. Expression of immunohistochemical markers was demonstrated to be associated with tumour progression and metastasis. The expression of p53, CD44 (splice variants v5, v6 and v9), E-cadherin, Ep-CAM (CO17-1A antigen) and c-erB2/neu were investigated in tumour tissues of 300 patients from the Dutch Gastric Cancer Trial, investigating the value of extended lymphadenectomy compared to that of limited lymphadenectomy). The expression of tumour markers was analysed with respect to patient survival. Patients without loss of Ep-CAM-expression of tumour cells (19%) had a significantly better 10-year survival (P<0.0001) compared to patients with any loss: 42% (s.e.=7%) vs 22% (s.e.=3%). Patients with CD44v6 (VFF18) expression in more than 25% of the tumour cells (69% of the patients) also had a significantly better survival (P=0.01) compared to patients with expression in less than 25% of the tumour cells: 10 year survival rate of 29% (s.e.=3%) vs 19% (s.e.=4%). The prognostic value of both markers was stronger in stages I and II, and independent of the TNM stage. Ep-CAM and CD44v6-expression provides prognostic information additional to the TNM stage. Loss of Ep-CAM-expression identifies aggressive tumours especially in patients with stage I and II disease. This information may be helpful in selecting patients suitable for surgery or for additional treatment pre- or postoperatively.
胃癌的术前分期困难且不理想。TNM分期是一个重要的预后因素,但只有在手术后才能可靠评估。因此,需要额外的、可靠的预后因素,以便在术前确定,从而挑选出可能从(新)辅助治疗中获益的患者。免疫组化标志物的表达已被证明与肿瘤进展和转移相关。在荷兰胃癌试验的300例患者的肿瘤组织中研究了p53、CD44(剪接变体v5、v6和v9)、E-钙黏蛋白、Ep-CAM(CO17-1A抗原)和c-erB2/neu的表达,该试验比较了扩大淋巴结清扫术与有限淋巴结清扫术的价值。分析了肿瘤标志物表达与患者生存率的关系。与有任何Ep-CAM表达缺失的患者相比,肿瘤细胞无Ep-CAM表达缺失的患者(19%)10年生存率显著更高(P<0.0001):分别为42%(标准误=7%)和22%(标准误=3%)。肿瘤细胞中CD44v6(VFF18)表达超过25%的患者(占患者的69%)与肿瘤细胞中表达低于25%的患者相比,生存率也显著更高(P=0.01):10年生存率分别为29%(标准误=3%)和19%(标准误=4%)。这两种标志物的预后价值在I期和II期更强,且独立于TNM分期。Ep-CAM和CD44v6表达提供了TNM分期之外的预后信息。Ep-CAM表达缺失可识别侵袭性肿瘤,尤其是I期和II期疾病患者。该信息可能有助于挑选适合手术或术前或术后接受额外治疗的患者。