Chen Zhouxun, Mustafa Tarek, Trojanowicz Bogusz, Brauckhoff Michael, Gimm Oliver, Schmutzler Cornelia, Köhrle Josef, Holzhausen Hans-Jürgen, Kehlen Astrid, Klonisch Thomas, Finke Rainer, Dralle Henning, Hoang-Vu Cuong
Department of General, Visceral and Vascular Surgery, Martin-Luther-University Halle-Wittenberg, Magdeburger Strasse 18, D-06097 Halle, Germany.
Int J Mol Med. 2004 Oct;14(4):517-27.
CD82 (KAI1) and CD63 (ME491) are highly glycosylated proteins which belong to the transmembrane 4 superfamily (TM4SF). CD82 has been implicated as a possible prostate cancer metastasis suppressor gene, whereas CD63 is involved in the progression of human melanoma cancer. Down-regulation of both CD82 and CD63 expression has been associated with the metastatic potential of several solid tumors. Currently, information is lacking on the role of CD82 and CD63 during thyroid carcinogenesis. The aim of this study was to determine whether the expression of CD82 and CD63 is a useful prognostic indicator in patients with thyroid carcinoma. The expression of CD82 and CD63 was analysed by reverse transcriptase-PCR (RT-PCR) and immunohistochemistry in benign goiter (n=12) and 75 primary thyroid carcinoma tissue specimens (PTC: 33, FTC: 24, UTC: 18) out of which 36 were non-metastasized primary tumors and 39 were metastasized tumors (regional lymph node and/or distant metastases). All of the benign goiter tissues showed CD82 expression. By contrast, a significant decrease in CD82 mRNA and protein levels was detected in carcinoma tissues as compared to benign goiter tissues (p<0.001). A similar down-regulation was observed in metastasized tumor tissues when compared with non-metastasized tumors (all p<0.05). CD82 expression was correlated with pTNM status of differentiated and undifferentiated thyroid tumor and the pathologic stage of differentiated thyroid tumor. In contrast to CD82, CD63 mRNA and protein expression was unchanged in all thyroid carcinomas. Benign goiter tissues showed weak expression of CD63. There were no significant correlation between CD63 mRNA/protein expression and any clinical/pathological parameters. Our results support the hypothesis that down-regulation of CD82 expression may reflect an increased in vivo metastatic potential of thyroid cancer cells. CD82 may serve as a prognostic marker of metastasis in thyroid cancer. Constitutive expression of CD63 may indicate that this factor does not play a direct role in thyroid carcinogenesis.
CD82（KAI1）和CD63（ME491）是高度糖基化的蛋白质，属于跨膜4超家族（TM4SF）。CD82被认为可能是一种前列腺癌转移抑制基因，而CD63则参与人类黑色素瘤的进展。CD82和CD63表达的下调与几种实体瘤的转移潜能有关。目前，关于CD82和CD63在甲状腺癌发生过程中的作用尚缺乏相关信息。本研究的目的是确定CD82和CD63的表达是否是甲状腺癌患者有用的预后指标。通过逆转录聚合酶链反应（RT-PCR）和免疫组织化学分析了12例良性甲状腺肿和75例原发性甲状腺癌组织标本（乳头状甲状腺癌：33例，滤泡状甲状腺癌：24例，未分化甲状腺癌：18例）中CD82和CD63的表达，其中36例为无转移的原发性肿瘤，39例为有转移的肿瘤（区域淋巴结和/或远处转移）。所有良性甲状腺肿组织均显示CD82表达。相比之下，与良性甲状腺肿组织相比，癌组织中检测到CD82 mRNA和蛋白水平显著降低（p<0.001）。与无转移肿瘤相比，转移瘤组织中也观察到类似的下调（所有p<0.05）。CD82表达与分化型和未分化型甲状腺肿瘤的pTNM状态以及分化型甲状腺肿瘤的病理分期相关。与CD82相反，所有甲状腺癌中CD63 mRNA和蛋白表达均无变化。良性甲状腺肿组织显示CD63弱表达。CD63 mRNA/蛋白表达与任何临床/病理参数之间均无显著相关性。我们的结果支持以下假设：CD82表达的下调可能反映甲状腺癌细胞体内转移潜能的增加。CD82可能作为甲状腺癌转移的预后标志物。CD63的组成性表达可能表明该因子在甲状腺癌发生中不发挥直接作用。
