Kusafuka Kimihide, Nakano Keisuke, Hiraki Yuji, Shukunami Chisa, Nagatsuka Hitoshi, Nagai Noriyuki, Takemura Tamiko, Sakaguchi Yutaku, Okazaki Kazuichi, Kusafuka Michi, Hisha Hiroko, Ikehara Susumu
Department of Transplantation for Regeneration Therapy, sponsored by Otsuka Pharmaceutical Co. Ltd., Kansai Medical University, Moriguchi City, 570-8506 Osaka, Japan.
Virchows Arch. 2005 Jan;446(1):34-40. doi: 10.1007/s00428-004-1125-y. Epub 2004 Nov 11.
Pleomorphic adenoma is the most common epithelial tumor in the salivary glands. This tumor frequently exhibits "mesenchyme"-like components, including myxoid or chondroid areas. Recently, using immunohistochemical techniques, we reported that cartilage-specific matrix protein, chondromodulin-I (ChM-I), was deposited on the inter-territorial matrix of the chondroid area in salivary pleomorphic adenomas and that ChM-I, which is also a strong angio-inhibitory factor, plays an important role in the avascular nature of the chondroid area and the chondroid formation in this type of tumor. To elucidate which cells express ChM-I mRNA in pleomorphic adenomas, we examined the expression and localization of ChM-I mRNA in this type of tumor using an in situ hybridization technique. Immunoreactivity for ChM-I was observed in the inter-territorial matrix of the chondroid area, especially around the lacunae, and in the cytoplasm of neoplastic myoepithelial cells of the myxoid element of pleomorphic adenomas. On in situ hybridization analysis, strong signals for ChM-I mRNA were detected in the cytoplasm of the lacuna cells of the chondroid element, and moderate to marked signals were observed in the cytoplasm of the neoplastic myoepithelial cells of the myxoid element. Signals for ChM-I mRNA were also seen in the cytoplasm of the spindle-shaped neoplastic myoepithelial cells in the transitional areas between the myxoid and chondroid elements of this tumor. Signals for ChM-I mRNA were not seen in the inner ductal cells or the fibrous element. These findings indicate that lacuna cells and neoplastic myoepithelial cells express ChM-I mRNA and that mature ChM-I, which lacuna cells and neoplastic myoepithelial cells translate, is deposited in the chondroid matrix of pleomorphic adenomas. In conclusion, lacuna cells and neoplastic myoepithelial cells express ChM-I mRNA ectopically in pleomorphic adenoma, and this plays an important role in chondroid formation and hypovascularity in this type of tumor.
多形性腺瘤是涎腺中最常见的上皮性肿瘤。该肿瘤常表现出“间充质”样成分,包括黏液样或软骨样区域。最近,我们运用免疫组化技术报告称,软骨特异性基质蛋白软骨调节素-I(ChM-I)沉积于涎腺多形性腺瘤软骨样区域的区域间基质中,并且ChM-I作为一种强大的血管抑制因子,在该类肿瘤软骨样区域的无血管特性及软骨样形成过程中发挥重要作用。为阐明多形性腺瘤中哪些细胞表达ChM-I mRNA,我们采用原位杂交技术检测了该类肿瘤中ChM-I mRNA的表达及定位情况。在软骨样区域的区域间基质中,尤其是在陷窝周围,以及多形性腺瘤黏液样成分的肿瘤性肌上皮细胞的细胞质中,观察到了ChM-I的免疫反应性。在原位杂交分析中,在软骨样成分陷窝细胞的细胞质中检测到ChM-I mRNA的强信号,在黏液样成分肿瘤性肌上皮细胞的细胞质中观察到中度至明显信号。在该肿瘤黏液样和软骨样成分之间过渡区域的梭形肿瘤性肌上皮细胞的细胞质中也可见ChM-I mRNA信号。在内导管细胞或纤维成分中未见到ChM-I mRNA信号。这些结果表明,陷窝细胞和肿瘤性肌上皮细胞表达ChM-I mRNA,并且陷窝细胞和肿瘤性肌上皮细胞翻译产生的成熟ChM-I沉积于多形性腺瘤的软骨样基质中。总之,陷窝细胞和肿瘤性肌上皮细胞在多形性腺瘤中异位表达ChM-I mRNA,这在该类肿瘤的软骨样形成和血管减少中起重要作用。