Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.
Histol Histopathol. 2010 Jan;25(1):63-72. doi: 10.14670/HH-25.63.
Reg IV (RELP), a Regenerating protein family member, is constitutively expressed in neuroendocrine cells of the intestinal mucosa. The helix-loop-helix transcription factor Hath1 is the human homologue of murine Math1, which regulates the embryonic differentiation of neural and intestinal secretory lineage cells. Hath1 is constitutively expressed in a subset of mature secretory gastrointestinal cells. We investigated by immunohistochemistry the expression of Reg IV and Hath1 in 63 neuroendocrine tumors. Intestinal neuroendocrine neoplasms showed co-expression of Reg IV and Hath1, as did parathyroidal and Merkel cell tumors. Lung small-cell carcinoma and gastric mucocellular carcinoma expressed only Reg IV. Pancreatic islet-derived tumors, pheochromocytomas, and paragangliomas expressed only Hath1. Lymph node and liver metastases retained the tissue-specific expression patterns. These distinct expression profiles may be useful for differential diagnostics of metastatic lesions of neuroendocrine tumors. The dissimilar expression patterns suggest that the proteins belong to different signaling pathways and are activated at different stages of neuroendocrine differentiation. Local Reg IV expression may be influenced by the growth factors bFGF and HGF and/or their receptors CD138 and c-met, which were found to co-localize with Reg IV in intestinal neuroendocrine tumors.
Reg IV（RELP）是再生蛋白家族的成员，在肠黏膜的神经内分泌细胞中持续表达。螺旋-环-螺旋转录因子 Hath1 是鼠类 Math1 的人类同源物，它调节神经和肠分泌谱系细胞的胚胎分化。Hath1 在成熟的分泌胃肠道细胞亚群中持续表达。我们通过免疫组织化学方法研究了 63 个神经内分泌肿瘤中 Reg IV 和 Hath1 的表达。肠神经内分泌肿瘤显示 Reg IV 和 Hath1 的共表达，甲状旁腺和 Merkel 细胞肿瘤也是如此。肺小细胞癌和胃黏液细胞癌仅表达 Reg IV。胰岛源性肿瘤、嗜铬细胞瘤和副神经节瘤仅表达 Hath1。淋巴结和肝转移保留了组织特异性表达模式。这些不同的表达谱可能有助于神经内分泌肿瘤转移灶的鉴别诊断。不同的表达模式表明这些蛋白质属于不同的信号通路，并在神经内分泌分化的不同阶段被激活。局部 Reg IV 的表达可能受到生长因子 bFGF 和 HGF 及其受体 CD138 和 c-met 的影响，这些因子被发现与肠神经内分泌肿瘤中的 Reg IV 共定位。
