Udagawa Hibiki, Ishii Genichiro, Morise Masahiro, Umemura Shigeki, Matsumoto Shingo, Yoh Kiyotaka, Niho Seiji, Ohmatsu Hironobu, Tsuboi Masahiro, Goto Koichi, Ochiai Atsushi, Ohe Yuichiro
Pathology Division, Department of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, 277-8577, Japan.
J Cancer Res Clin Oncol. 2015 Aug;141(8):1417-25. doi: 10.1007/s00432-015-1912-7. Epub 2015 Jan 9.
Immunohistochemical analysis for the identification of clinically relevant biomarkers is important. However, there have been no detailed reports about the heterogeneous expressions of the various markers in squamous cell carcinoma of the lung.
A total of 113 patients with squamous cell carcinoma of the lung with lymph node metastasis were included. The expression levels of 9 molecules (E-cadherin, S100A4, CD44, ALDH1, SOX2, EGFR, HER2, FGFR1 and VEGFR2) in the peripheral area and central area of primary tumor and metastatic lymph nodes were evaluated by immunohistochemistry. The differences in the staining scores of these molecules among the three areas were assessed. We also analyzed the relationships between the expression levels of these molecules and the recurrence-free survival.
The E-cadherin expression was higher in the central area than in the peripheral area and metastatic lymph nodes (median staining score: 60 vs. 50, 30); the CD44 expression was higher in the central area than in the metastatic lymph nodes (117 vs. 90); and the EGFR expression was higher in the central area than in the peripheral area and metastatic lymph nodes (163 vs. 130, 110). Low CD44 expression in the central area, low EGFR expression in the peripheral area and high SOX2 expression in the metastatic lymph nodes were associated with a shorter recurrence-free survival (p < 0.01, p = 0.02, p = 0.03, respectively).
Our findings confirmed that some molecular markers exhibited different expression levels in anatomically different areas and suggested that area-by-area immunohistochemical analysis for biomarkers may provide useful information for more precise prediction of the recurrence.
免疫组化分析对于识别临床相关生物标志物很重要。然而,关于肺鳞状细胞癌中各种标志物的异质性表达尚无详细报道。
纳入113例伴有淋巴结转移的肺鳞状细胞癌患者。通过免疫组化评估9种分子(E-钙黏蛋白、S100A4、CD44、醛脱氢酶1、SOX2、表皮生长因子受体、人表皮生长因子受体2、成纤维细胞生长因子受体1和血管内皮生长因子受体2)在原发性肿瘤及转移淋巴结周边区域和中央区域的表达水平。评估这9种分子在三个区域的染色评分差异。我们还分析了这些分子的表达水平与无复发生存率之间的关系。
E-钙黏蛋白在中央区域的表达高于周边区域和转移淋巴结(中位染色评分:60对50、30);CD44在中央区域的表达高于转移淋巴结(117对90);表皮生长因子受体在中央区域的表达高于周边区域和转移淋巴结(163对130、110)。中央区域低CD44表达、周边区域低表皮生长因子受体表达以及转移淋巴结高SOX2表达与较短的无复发生存率相关(分别为p<0.01、p = 0.02、p = 0.03)。
我们的研究结果证实,一些分子标志物在解剖学上不同的区域表现出不同的表达水平,并表明对生物标志物进行逐个区域的免疫组化分析可能为更精确地预测复发提供有用信息。