Wang Liang-Shun, Chow Kuan-Chih, Lien Yung-Chang, Kuo Kuang-Tai, Li Wing-Yin
Division of Thoracic Surgery, Department of Surgery, Taipei-Veterans General Hospital and National Yang-Ming University, 201, Sec. 2, Shih-Pai Road, Taipei 112, Taiwan, ROC.
Eur J Cardiothorac Surg. 2004 Aug;26(2):419-24. doi: 10.1016/j.ejcts.2004.03.045.
Tumor recurrence and metastasis are major causes of treatment failure in esophageal squamous cell carcinoma (ESCC). Recently, nm23, originally considered to be an anti-metastatic gene, has been reported to associate with various roles in different human cancers. We therefore investigated the clinical significance of nm23-H1 expression in ESCC.
Pathological sections were immunohistochemically stained with monoclonal antibody that was specific to nm23-H1. Expression of positive nm23-H1 staining was further confirmed by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). The relationship between nm23-H1 expression and clinicopathological variables was examined by statistical analysis. Except for 11 (7%) surgical morality, the remaining 145 patients entered the prognostic analysis. The cisplatin-based chemotherapy was established for the patients with tumor stages at or beyond IIb, or with tumor recurrence. Survival difference between groups was compared by log rank test.
Immunohistochemically, nm23-H1 expression was detected in 39.3% (57/145) of the pathological sections. It was positively correlated with tumor stage (P = 0.002), evident lymphovascular invasion (P < 0.001) and tumor recurrence (P = 0.02). Survival of nm23-H1 positive group was statistically superior to nm23-H1 negative group (P < 0.0001) By multivariate survival analysis, tumor stage, the number of lymph node metastasis and expression of nm23-H1 were the independent prognostic factors for ESCC patients.
Our study demonstrated that nm23-H1 expression was associated with disease progression in ESCC. However, survival of nm23-H1 positive group was superior to nm23-H1 negative group. This paradoxical result could suppose that nm23-H1 expression might increase cisplatin chemosensitivity and hence improve survival. Screening for nm23-H1 expression in tumor cells may be a potential therapeutic strategy in ESCC patients.
肿瘤复发和转移是食管鳞状细胞癌(ESCC)治疗失败的主要原因。最近,nm23最初被认为是一种抗转移基因,据报道在不同的人类癌症中具有多种作用。因此,我们研究了nm23-H1在ESCC中的表达的临床意义。
病理切片用对nm23-H1特异的单克隆抗体进行免疫组织化学染色。通过蛋白质印迹法和逆转录-聚合酶链反应(RT-PCR)进一步证实nm23-H1阳性染色的表达。通过统计分析检查nm23-H1表达与临床病理变量之间的关系。除11例(7%)手术死亡率外,其余145例患者进入预后分析。对于肿瘤分期为IIb期及以上或有肿瘤复发的患者,采用以顺铂为基础的化疗。通过对数秩检验比较组间生存差异。
免疫组织化学检测显示,145例病理切片中有39.3%(57/145)检测到nm23-H1表达。它与肿瘤分期(P = 0.002)、明显的淋巴管浸润(P < 0.001)和肿瘤复发(P = 0.02)呈正相关。nm23-H1阳性组的生存率在统计学上优于nm23-H1阴性组(P < 0.0001)。通过多因素生存分析,肿瘤分期。淋巴结转移数量和nm23-H1表达是ESCC患者的独立预后因素。
我们的研究表明nm23-H1表达与ESCC的疾病进展相关。然而,nm23-H1阳性组的生存率优于nm23-H1阴性组。这一矛盾的结果可能表明nm23-H1表达可能增加顺铂化疗敏感性,从而提高生存率。检测肿瘤细胞中nm23-H1表达可能是ESCC患者的一种潜在治疗策略。