Abstract:
Tumors of the head and neck, more specifically the squamous cell carcinoma, often show upregulation of the Hedgehog signaling pathway. However, almost nothing is known about its role in the sinonasal adenocarcinoma, either in intestinal or non-intestinal subtypes. In this work, we have analyzed immunohistochemical staining of six Hedgehog pathway proteins, sonic Hedgehog (SHH), Indian Hedgehog (IHH), Patched1 (PTCH1), Gli family zinc finger 1 (GLI1), Gli family zinc finger 2 (GLI2), and Gli family zinc finger 3 (GLI3), on 21 samples of sinonasal adenocarcinoma and compared them with six colon adenocarcinoma and three salivary gland tumors, as well as with matching healthy tissue, where available. We have detected GLI2 and PTCH1 in the majority of samples and also GLI1 in a subset of samples, while GLI3 and the ligands SHH and IHH were generally not detected. PTCH1 pattern of staining shows an interesting pattern, where healthy samples are mostly positive in the stromal compartment, while the signal shifts to the tumor compartment in tumors. This, taken together with a stronger signal of GLI2 in tumors compared to non-tumor tissues, suggests that the Hedgehog pathway is indeed activated in sinonasal adenocarcinoma. As Hedgehog pathway inhibitors are being tested in combination with other therapies for head and neck squamous cell carcinoma, this could provide a therapeutic option for patients with sinonasal adenocarcinoma as well.
摘要:
头部和颈部的肿瘤,更具体地说是鳞状细胞癌,通常显示Hedgehog信号通路的上调。然而,几乎没有人知道它在鼻窦腺癌中的作用,无论是在肠道或非肠道亚型。在这项工作中,我们分析了六种Hedgehog通路蛋白的免疫组织化学染色,索尼克刺猬(SHH),印度刺猬(IHH),Patched1(PTCH1),Gli家族锌指1(GLI1),Gli家族锌指2(GLI2),和Gli家族锌指3(GLI3),对21例鼻腔鼻窦腺癌样本进行比较,并与6例结肠腺癌和3例涎腺肿瘤进行比较,以及匹配的健康组织,可用的地方。我们在大多数样品中检测到GLI2和PTCH1,在一部分样品中检测到GLI1,而GLI3和配体SHH和IHH通常未检测到。PTCH1染色模式显示了一个有趣的模式,健康样本在基质室中大部分是阳性的,而信号转移到肿瘤的肿瘤区室。这个,与非肿瘤组织相比,肿瘤中的GLI2信号更强,提示Hedgehog通路在鼻窦腺癌中确实被激活。由于Hedgehog通路抑制剂正在与其他治疗头颈部鳞状细胞癌的疗法联合进行测试,这也可以为鼻窦腺癌患者提供治疗选择.