Ito Reiko, Nakayama Hirofumi, Yoshida Kazuhiro, Kuraoka Kazuya, Motoshita Junichi, Oda Noriko, Oue Naohide, Yasui Wataru
Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Japan.
Virchows Arch. 2003 Aug;443(2):146-51. doi: 10.1007/s00428-003-0845-8. Epub 2003 Jun 28.
Osteoprotegerin (OPG), identical with osteoclastogenesis inhibitory factor, is a member of a subgroup of the tumor necrosis factor (TNF)-receptor superfamily, which functions as a soluble decoy receptor. It has been reported that OPG expression is associated with bone metastasis of cancer of the breast and prostate. In the present study, we examined the expression of OPG in gastric carcinomas using immunohistochemistry and reverse-transcription polymerase chain reaction methods, and compared with clinicopathological parameters. The expression of OPG mRNA was confirmed in a gastric carcinoma cell line (MKN-7) and gastric carcinoma tissues. Immunohistochemically, strongly positive staining of OPG was found in 65% (67/103) of gastric carcinomas, whereas OPG protein was not detected in non-neoplastic mucosal epithelia. The expression of OPG protein in gastric carcinoma tissues correlates significantly with depth of tumor invasion, nodal metastases and advanced tumor stage. Furthermore, the prognosis of the cases with strong OPG expression was significantly worse than those with weak or no expression of OPG. These results suggest that OPG may participate in stomach carcinogenesis, invasion and metastasis, and may serve as a novel molecular marker for aggressive gastric cancer.
骨保护素（OPG）与破骨细胞生成抑制因子相同，是肿瘤坏死因子（TNF）受体超家族一个亚组的成员，其作为一种可溶性诱饵受体发挥作用。据报道，OPG的表达与乳腺癌和前列腺癌的骨转移有关。在本研究中，我们采用免疫组织化学和逆转录聚合酶链反应方法检测了OPG在胃癌中的表达，并与临床病理参数进行了比较。在胃癌细胞系（MKN-7）和胃癌组织中证实了OPG mRNA的表达。免疫组织化学检测发现，65%（67/103）的胃癌中OPG呈强阳性染色，而在非肿瘤性黏膜上皮中未检测到OPG蛋白。胃癌组织中OPG蛋白的表达与肿瘤浸润深度、淋巴结转移及肿瘤晚期显著相关。此外，OPG强表达病例的预后明显差于OPG弱表达或无表达的病例。这些结果表明，OPG可能参与胃癌的发生、侵袭和转移，并且可能作为侵袭性胃癌的一种新型分子标志物。
