Recruitment of Podoplanin Positive Cancer-Associated Fibroblasts in Metastatic Lymph Nodes Predicts Poor Prognosis in Pathological N2 Stage III Lung Adenocarcinoma
Recruitment of Podoplanin Positive Cancer-Associated Fibroblasts in Metastatic Lymph Nodes Predicts Poor Prognosis in Pathological N2 Stage III Lung Adenocarcinoma
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DOI：
10.1245/s10434-012-2421-4
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发表时间：
2012-11-01
影响因子：
3.7
通讯作者：
Ochiai, Atsushi
中科院分区：
文献类型：
--
作者：
Neri, Shinya;Ishii, Genichiro;Ochiai, Atsushi
癌症相关成纤维细胞（CAF）直接与癌细胞沟通，在癌症进展中发挥重要作用。最近的研究报道，具有表达podoplanin的CAF的原发癌组织预测I期肺腺癌患者的预后较差。然而，在这方面，Podoplanin（+）-CAFs是否也能被募集到转移性淋巴结中并影响预后尚不清楚。我们选择了112例病理学N2期III期肺腺癌患者，检测了CAFs的Podoplanin表达及其对原发性和转移性N2病变预后的影响。在61例N2期肺腺癌患者中观察到Podoplanin（+）-CAFs，原发部位54.5%，转移淋巴结44个（39.3%）。在33例（54.1%）原发性podoplanin阳性和11例（21.6%）原发性podoplanin阴性的转移淋巴结中发现Podoplanin（+）-CAF。这些结果表明podoplanin在CAFs中的表达在原发灶和转移灶之间呈显著正相关（P < 0.001）。在原发病变中podoplanin阳性/阴性CAF患者的总生存率差异不相关（P = 0.927）。相比之下，在转移性淋巴结中具有podoplanin（+）-CAF的患者的总生存期比不具有podoplanin（+）-CAF的患者短（P = 0.003）。在多变量分析中，转移淋巴结中的podoplanin（+）-CAFs是预后不良的显著独立危险因素（P = 0.007）。我们的研究表明，转移淋巴结中的podoplanin（+）-CAFs是病理N2期III腺癌患者总生存率的显著预后因素。
Cancer-associated fibroblasts (CAFs) directly communicate with cancer cells and play important roles in cancer progression. Recent studies have reported that primary cancer tissue with podoplanin-expressing CAFs predicted a poorer outcome among stage I lung adenocarcinoma patients. However, whether podoplanin(+)-CAFs also can be recruited into metastatic lymph nodes and influence the prognosis remains unclear.We selected 112 patients with pathological N2 stage III lung adenocarcinoma and examined the podoplanin expression of CAFs and their prognostic impact in primary and metastatic N2 lesions.Podoplanin(+)-CAFs were observed in 61 (54.5 %) primary sites and 44 (39.3 %) metastatic lymph nodes. Podoplanin(+)-CAFs were found at metastatic lymph nodes in 33 (54.1 %) primary podoplanin-positive and 11 (21.6 %) primary podoplanin-negative sites. These findings suggest a significant positive correlation in podoplanin expression in CAFs between pairs of primary and metastatic lesions (P < 0.001). The difference in the overall survival of patients with podoplanin-positive/negative CAFs in their primary lesion was not correlated (P = 0.927). In contrast, patients with podoplanin(+)-CAFs in metastatic lymph nodes had a shorter overall survival than those without podoplanin(+)-CAFs (P = 0.003). In multivariate analyses, podoplanin(+)-CAFs in metastatic lymph nodes were a significantly independent risk factor for a poor outcome (P = 0.007).Our study indicated that podoplanin(+)-CAFs in metastatic lymph nodes was a significant prognostic factor for overall survival among pathological N2 stage III adenocarcinoma patients.