Ma Wei, Wang Kai, Yang Shaoqi, Wang Jianbo, Tan Bingxu, Bai Bing, Wang Nana, Jia Yibin, Jia Ming, Cheng Yufeng
Department of Radiation Oncology, Qilu Hospital of Shandong University Jinan, China ; Department of Radiation Oncology, Cancer Hospital, General Hospital of Ningxia Medical University Yinchuan, China.
Department of Oncology, Wendeng Central Hospital Weihai, China.
Int J Clin Exp Pathol. 2014 Apr 15;7(5):2361-71. eCollection 2014.
Podoplanin (D2-40) is a specific marker for lymphatic endothelium. The vast majority of previous studies on podoplanin immunostaining in esophageal squamous cell carcinoma (ESCC) focused on identifying lymphatic vessel invasion (LVI) and counting lymphatic vessel density (LVD) and had contradictory results. Recent studies show podoplanin expression on cancer cells or tumor stroma in several cancers, which have specific significance; but the status in ESCC remains unclear. Therefore, the aim of this study was to further study and summarize the clinicopathological significance of podoplanin immunoreactivity in ESCC.
We examined podoplanin expression in tissue specimens from 107 patients with ESCC by immunohistochemistry. Podoplanin positive lymphatic vessels in intratumoral and peritumoral tissues and podoplanin positive expression in cancer cells and tumor stroma were analyzed, and correlated with clinicopathologic parameters and three-year overall and free-disease survival.
34 (31.8%) and 28 (26.2%) of 107 specimens had podoplanin positive expression in cancer cells and tumor stroma, respectively. Logistic regression analysis showed high intratumoral lymphatic vessel density (I-LVD) and podoplanin positivity in cancer cells were increased risks of lymph node metastasis (LNM) (OR=2.45, P=0.03; OR=0.35, P=0.01, respectively). Survival analysis showed that I-LVD was a significant factor related to poor three-year overall and free-disease survival (P=0.04, P=0.03, respectively).
Previous data and our results show that podoplanin seems to be a useful marker to predict LNM, recurrence, and worse prognosis in ESCC; in particular, LVI, high I-LVD, and podoplanin positivity in cancer cells are associated with LNM, recurrence and overall survival.
血小板源性生长因子受体(Podoplanin,D2-40)是淋巴管内皮细胞的特异性标志物。既往绝大多数关于食管鳞状细胞癌(ESCC)中Podoplanin免疫染色的研究集中于识别淋巴管侵犯(LVI)和计数淋巴管密度(LVD),但结果相互矛盾。近期研究显示Podoplanin在几种癌症的癌细胞或肿瘤基质中表达,具有特定意义;但其在ESCC中的情况仍不清楚。因此,本研究的目的是进一步研究并总结Podoplanin免疫反应性在ESCC中的临床病理意义。
我们采用免疫组化法检测了107例ESCC患者组织标本中Podoplanin的表达。分析肿瘤内和肿瘤周围组织中Podoplanin阳性淋巴管以及癌细胞和肿瘤基质中Podoplanin阳性表达情况,并与临床病理参数及三年总生存率和无病生存率进行相关性分析。
107例标本中分别有34例(31.8%)和28例(26.2%)癌细胞及肿瘤基质中Podoplanin呈阳性表达。Logistic回归分析显示,肿瘤内淋巴管密度(I-LVD)高及癌细胞中Podoplanin阳性是淋巴结转移(LNM)风险增加的因素(OR分别为2.45,P=0.03;OR为0.35,P=0.01)。生存分析显示,I-LVD是与三年总生存率和无病生存率差相关的重要因素(P分别为0.04,P=0.03)。
既往数据及我们的结果表明,Podoplanin似乎是预测ESCC中LNM、复发及不良预后的有用标志物;特别是LVI高、I-LVD高及癌细胞中Podoplanin阳性与LNM、复发及总生存相关。