肿瘤相关成纤维细胞中平足蛋白的表达与组织浸润血小板在浸润性乳腺癌预后判断中的应用

Association of podoplanin - expressing cancer - associated fibroblasts and platelet infiltration with poor prognosis in invasive breast cancer

目的探讨过表达平足蛋白（PDPN）的肿瘤相关成纤维细胞（CAFs）和肿瘤浸润血小板在乳腺癌预后判断中的作用。方法收集行乳腺癌根治术的164例浸润性乳腺导管癌患者，通过D2-40和CD61单抗免疫组织化学法分别检测CAFs中PDPN和肿瘤组织中血小板浸润的表达，并获取所有患者术前血小板计数，统计学分析这些指标在乳腺癌预后判断中的作用。结果免疫组织化学显乐72例（44％）患者的CAFs中存在PDPN的表达（CAF^＋），而在57例（35％）患者中显示有血小板的浸润（CD61^＋）。相关分析显示有多个因素间呈显著性相关，其中CAF^＋与临床分期明显相关（P=0．049），CD61^＋与术前血小板计数（P=0．004）和CAF^＋与CD61^＋（P=0．048）。单因素生存分析显示CAF^＋，CD61^＋和术前血小板计数大于280×10^9／L组的无病生存期（DFS）明显低于对照组，P值分别为0．001、0．024和0．027。而在多因素生存分析中显示CAF^＋是一个独立的不良预后因素[风险比（HR）值=3．928；P=0．005]。结论CAF^＋和CD61^＋均是浸润型乳腺导管癌的不良预后因素，同时CD61^＋与术前外周血血小板的计数明显相关。

Objective To investigate the prognostic role of podoplanin （PDPN） expressing cancerassociated fibroblasts （CAFs） and the infiltration of platelets into tumors in breast invasive ductal carcinoma. Methods A total of 164 patients were included in the study at the time of primrose surgery for invasive breast cancer between January 2007 and Decemher ：2008 from the Affiliated Hospital of Jiangnan University. The PI）PN expression in CAFs and the infiltration of platelets in tumor tissue was evaluated by inmmnohistochemistry respectively with mouse monoclonal anti -human PDPN （clon： D2 -40） and mouse monoclonal anti - human CD61. The platelet count before surgery was also measured. The prognostic role of these indicators in invasive breast cancer was statistically analyzed. ResuLts Seventy - two patients （44%） showed PDPN expression in CAFs （CAF^＋ ）, while 47 patients （35%） showed the infiltration of platelets in tumor tissue （CD61^＋ ）. Several strong positive correlations were found, including CAF^＋ with clinical stage （P=0. 049）, CD61^＋ with blood platelet counts before surgery （P=0.004）, and CAF^＋ with CD61^ ＋ （ P = 0. 048 ）. The univariate analysis revealed that the patients with CAF^＋ , CD61^＋ or platelet counts 〉 280 × 10^9/L before surgery had a significantly shorter disease -free survival according to univariate analysis （P value was 0. 001 , 0. 024 and 0. 027 respectively）. The muhivariable analysis showed that CAF^＋ was an independent prognostic factor （ Hazard ratio = 3. 928 ;P = 0. 005 ）. Conclusion CAF^＋ and CD61^＋ were tound to be good prognosis factors for invasive breast cancer patients. CD61^＋ had a strong positive correlation with blood platelet counts betore surgery.