Matsumura Yoshiyuki, Hiraoka Kei, Ishikawa Keidai, Shoji Yasuhito, Noji Takehiro, Hontani Koji, Itoh Tomoo, Nakamura Toru, Tsuchikawa Takahiro, Shichinohe Toshiaki, Hirano Satoshi
Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Anticancer Res. 2016 Sep;36(9):4467-75. doi: 10.21873/anticanres.10991.
The co-stimulatory molecule cluster of differentiation 40 (CD40) is widely expressed in various types of malignant tumors, but its role remains unclear. The purpose of this study was to investigate the relationship between CD40 expression and clinicopathological variables in patients with esophageal squamous cell carcinoma (ESCC), as well as the function of CD40 expressed on ESCC tumor cells in vitro.
Tumor specimens of patients who underwent surgical resection for ESCC were immunohistochemically analyzed for CD40 expression.
Of the 122 specimens, 45 (37%) were positive for CD40. Significant positive correlation was found between CD40 expression and p-stage (p=0.0011), histopathological grade (p=0.0143), pT-classification (p=0.0011), and pN-classification (p=0.0007). Survival of patients with stage III and IV disease with positive CD40 expression was significantly shorter than that of those with negative expression (log-rank test, p=0.0422). In in vitro analysis, while the addition of recombinant human CD154 did not inhibit growth, it did induce a significant increase in interleukin 6 production in ESCC cell lines.
These results suggest that functional expression of CD40 on tumor cells might play an important role in tumor progression and lymph node metastasis in ESCC.
共刺激分子分化簇40（CD40）在多种类型的恶性肿瘤中广泛表达，但其作用仍不清楚。本研究旨在探讨食管鳞状细胞癌（ESCC）患者中CD40表达与临床病理变量之间的关系，以及ESCC肿瘤细胞上表达的CD40在体外的功能。
对接受ESCC手术切除的患者的肿瘤标本进行CD40表达的免疫组织化学分析。
在122份标本中，45份（37%）CD40呈阳性。发现CD40表达与p分期（p = 0.0011）、组织病理学分级（p = 0.0143）、pT分类（p = 0.0011）和pN分类（p = 0.0007）之间存在显著正相关。CD40表达阳性的III期和IV期疾病患者的生存期明显短于表达阴性的患者（对数秩检验，p = 0.0422）。在体外分析中，虽然添加重组人CD154不会抑制生长，但它确实会诱导ESCC细胞系中白细胞介素6的产生显著增加。
这些结果表明，肿瘤细胞上CD40的功能性表达可能在ESCC的肿瘤进展和淋巴结转移中起重要作用。
