Kawase Akikazu, Ishii Genichiro, Nagai Kanji, Ito Takeo, Nagano Tatsuya, Murata Yukinori, Hishida Tomoyuki, Nishimura Mitsuyo, Yoshida Junji, Suzuki Kazuya, Ochiai Atsushi
Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Int J Cancer. 2008 Sep 1;123(5):1053-9. doi: 10.1002/ijc.23611.
Recent studies have reported increased podoplanin expression by cancer cells and stromal cells, but little is known about its expression and biological significance in adenocarcinoma of the lung. We examined podoplanin expression by both cancer cells and stromal cells in 177 consecutive lung adenocarcinoma cases and analyzed relations between podoplanin expression and both clinicopathological factors and outcome. Podoplanin expression was observed on the apical membrane of the cancer cells in only 9 of the 177 (5.1%) cases. By contrast, cancer-associated fibroblasts (CAFs) were found to express podoplanin in 54 cases (30.5%). Podoplanin (+) CAFs were found only in invasive adenocarcinoma and none were found in noninvasive adenocarcinoma. Conventional prognostic factors were significantly correlated with podoplanin expression by CAFs. The univariate analyses and log-rank test showed that podoplanin expression was significantly associated with shorter survival time (p < 0.001 and p < 0.001, respectively). We divided the cases into 3 groups according grade based on the proportion of CAFs expressing podoplanin [a grade 0 group (n = 123), a grade 1 group (n = 36) and a grade 2 group (n = 18)]. The result showed that conventional prognostic factors were significantly correlated with the grade of podoplanin expression by CAFs. Furthermore, the grade 2 group tended to have a shorter survival time than the grade 1 group (p = 0.092). The results of this study highlight the importance of podoplanin expression by CAFs and provide new insights into the biology of the cancer microenvironment in adenocarcinoma of the lung.
近期研究报道癌细胞和基质细胞中血小板反应蛋白-1表达增加，但对其在肺腺癌中的表达及生物学意义知之甚少。我们检测了177例连续的肺腺癌病例中癌细胞和基质细胞的血小板反应蛋白-1表达，并分析了血小板反应蛋白-1表达与临床病理因素及预后的关系。在177例病例中，仅9例（5.1%）癌细胞的顶端膜上观察到血小板反应蛋白-1表达。相比之下，54例（30.5%）病例中发现癌相关成纤维细胞（CAF）表达血小板反应蛋白-1。仅在浸润性腺癌中发现血小板反应蛋白-1（+）CAF，在非浸润性腺癌中未发现。传统预后因素与CAF的血小板反应蛋白-1表达显著相关。单因素分析和对数秩检验表明，血小板反应蛋白-1表达与较短的生存时间显著相关（分别为p < 0.001和p < 0.001）。我们根据表达血小板反应蛋白-1的CAF比例将病例分为3组[0级组（n = 123）、1级组（n = 36）和2级组（n = 18）]。结果表明，传统预后因素与CAF的血小板反应蛋白-1表达分级显著相关。此外，2级组的生存时间往往比1级组短（p = 0.092）。本研究结果突出了CAF中血小板反应蛋白-1表达的重要性，并为肺腺癌癌微环境生物学提供了新的见解。
