D2-40 表达测量的肿瘤内淋巴管密度而非肿瘤周围淋巴管密度预测胃癌不良预后——寻找截断点的 ROC 曲线分析。
Intratumoral but not peritumoral lymphatic vessel density measured by D2-40 expression predicts poor outcome in gastric cancer--ROC curve analysis to find cut-off point.
机构信息
Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland
Second Department of General and Oncological Surgery, Wroclaw Medical University, Wroclaw, Poland.
出版信息
Anticancer Res. 2014 Jun;34(6):3113-8.
BACKGROUND
Neolymphangiogenesis, a process of lymphatic vessel development in neoplastic tissue, may be a key event in the transmission of cancer cells into lymph nodes. The current study examined the relationship between lymphatic vessel density (LVD) measured by podoplanin (D2-40) expression, clinicopathological parameters and patient survival in gastric cancer.
MATERIALS AND METHODS
D2-40 expression was examined by immunohistochemistry in formalin-fixed paraffin-embedded tissue specimens obtained from 60 patients with gastric cancer. D2-40 immunoreactivity was analyzed in intratumoral and peritumoral compartments of tumors and correlated with tumor grade, type in Lauren's classification, lymph node status, distant metastasis, presence of ulceration, inflammatory infiltration, angio-invasion, lymphangio-invasion and patient survival using a Receiver Operating Characteristic (ROC) curve analysis to find cut-off points that enabled fair decision making in survival analysis.
RESULTS
The mean values of intratumoral and peritumoral LVD were 6.63 and 11.25, respectively. Enhanced intratumoral LVD measured by D2-40 immunoexpression was correlated with the presence of lymph node metastases (p=0.04). Our study revealed a statistically significant correlation between intratumoral LVD measured by D2-40 expression and survival of patients with gastric cancer: an intratumoral LVD higher than 4.68 is significantly correlated with unfavorable prognosis, with a probability of death of approximately 80%. No significant relationship was identified between peritumoral LVD, lymph node status and survival in patients with gastric cancer.
CONCLUSION
A high intratumoral LVD measured by D2-40 expression in specimens from primary tumors is strongly associated with lymph node metastasis and predicts worse clinical outcome. Increased intratumoral D2-40 immunoreactivity is a putative predictor of aggressive gastric cancer behavior.
背景
新淋巴管生成是肿瘤组织中淋巴管发育的过程，可能是癌细胞转移到淋巴结的关键事件。本研究探讨了在胃癌中，通过 podoplanin（D2-40）表达测量的淋巴管密度（LVD）与临床病理参数和患者生存之间的关系。
材料和方法
采用免疫组织化学方法检测 60 例胃癌患者福尔马林固定石蜡包埋组织标本中 D2-40 的表达。在肿瘤的瘤内和瘤周区域分析 D2-40 免疫反应性，并与肿瘤分级、Lauren 分类中的肿瘤类型、淋巴结状态、远处转移、溃疡形成、炎症浸润、血管侵犯、淋巴管侵犯以及患者生存相关，使用 ROC 曲线分析寻找能够在生存分析中进行公平决策的截止值。
结果
肿瘤内和肿瘤旁 LVD 的平均值分别为 6.63 和 11.25。通过 D2-40 免疫表达测量的增强的肿瘤内 LVD 与淋巴结转移的存在相关（p=0.04）。我们的研究表明，通过 D2-40 表达测量的肿瘤内 LVD 与胃癌患者的生存之间存在统计学显著相关性：肿瘤内 LVD 高于 4.68 与不良预后显著相关，死亡概率约为 80%。肿瘤旁 LVD、淋巴结状态与胃癌患者的生存之间未发现显著相关性。
结论
原发肿瘤标本中通过 D2-40 表达测量的高肿瘤内 LVD 与淋巴结转移密切相关，并预测临床结局较差。肿瘤内 D2-40 免疫反应性增加是侵袭性胃癌行为的潜在预测因子。
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