Expression of podoplanin, CD44, and p63 in squamous cell carcinoma of the lung
Expression of podoplanin, CD44, and p63 in squamous cell carcinoma of the lung
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DOI：
10.1111/j.1349-7006.2009.01295.x
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发表时间：
2009-11-01
期刊：
影响因子：
5.7
通讯作者：
Ochiai, Atsushi
中科院分区：
文献类型：
--
作者：
Shimada, Yoshihisa;Ishii, Genichiro;Ochiai, Atsushi
最近的分子生物学研究已将足足蛋白确定为鳞状细胞癌 (SqCC) 的候选癌症干细胞 (CSC) 标记物。本研究的目的是检查 podoplanin 以及其他干细胞标记物 CD44 和 p63 的表达模式，以及它们与临床病理特征（包括肺 SqCC 生存）的关系。我们通过免疫染色在组织学上检查了 162 个连续 SqCC 中足足蛋白、CD44 和 p63 的表达。分别在 107 个 (66%) 肿瘤中观察到平足蛋白表达，在 145 个肿瘤 (89.5%) 中观察到 CD44 表达，在 151 个肿瘤 (93.2%) 中观察到 p63 表达。在95.3%的平足蛋白阳性肿瘤中，强表达的肿瘤细胞位于瘤巢的外围。然而，仅在 55.9% 的 CD44 阳性肿瘤和 43% 的 p63 阳性肿瘤中观察到这种外周定位。在 88.8% 的平足蛋白阳性肿瘤中，阳性细胞比 CD44 或 p63 阳性细胞位于肿瘤巢的更外围，并且当比较这些平足蛋白阳性肿瘤中的 CD44 和 p63 表达时，肿瘤巢外围的 p63 阳性层比 CD44 阳性层更宽。这些发现表明肿瘤细胞根据这三种标记物的表达以“分层分布模式”排列。具有“分层模式”的 podoplanin 阳性肿瘤患者的总生存率明显高于患有 podoplanin 阴性肿瘤的患者 (P = 0.043)。这些结果表明，podoplanin的表达将反映SqCC分化过程中最不成熟的状态，并且基于CSC概念，具有分级表达的SqCC将是组织良好、生物侵袭性较低的肿瘤组。 （癌症科学 2009 年）。
Recent molecular biological studies have identified podoplanin as a candidate cancer stem cell (CSC) marker in squamous cell carcinoma (SqCC). The purpose of this study was to examine the expression pattern of podoplanin, and the other stem cell markers CD44 and p63, and their relationship to clinico-pathological features including survival in pulmonary SqCC. We examined histologically the expression of podoplanin, CD44, and p63 in 162 consecutive SqCC by immunostaining. Podoplanin expression was observed in 107 (66%) tumors, CD44 in 145 (89.5%), and p63 in 151 (93.2%), respectively. In 95.3% of the podoplanin-positive tumors, tumor cells showing strong expression were localized in the periphery of the tumor nests. However, this peripheral localization was observed in only 55.9% of the CD44-positive and 43% of p63-positive tumors. In 88.8% of the podoplanin-positive tumors, positive cells were localized more peripherally in the tumor nests than CD44- or p63-positive cells and when CD44 and p63 expressions were compared in these podoplanin-positive tumors, p63-positive layers in the periphery of the tumor nests were broader compared to CD44-positive layers. These findings suggest tumor cells are aligned in the "hierarchical distribution pattern" according to the expression of these three markers. Patients who had podoplanin-positive tumors with the "hierarchical pattern" resulted in significantly better overall survival than those who had podoplanin-negative tumors (P = 0.043). These results suggest that podoplanin expression would reflect the most immature status in the differentiation process of SqCC, and SqCC with hierarchical expression would be a well-organized tumor group with lower biological aggressiveness based on the CSC concept. (Cancer Sci 2009).