Sato Haruhiro, Ino Yoshinori, Miura Ayaka, Abe Yoshifumi, Sakai Hideto, Ito Koichi, Hirohashi Setsuo
Pathology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
J Clin Endocrinol Metab. 2003 Sep;88(9):4407-12. doi: 10.1210/jc.2002-021757.
Dysadherin is a cancer-associated cell membrane glycoprotein. Its cDNA encodes 178 amino acids, including a putative signal sequence, a potential O-glycosylated extracellular domain, a single transmembrane domain, and a short cytoplasmic tail. Dysadherin is believed to down-regulate the expression of E-cadherin, the prime mediator of cell-cell adhesion in epithelial cells, by a posttranscriptional mechanism and promote the metastasis of carcinoma cells. To evaluate the association between dysadherin expression and E-cadherin expression in thyroid carcinoma, immunostaining for dysadherin and E-cadherin was performed in 51 papillary, 10 follicular, and 31 undifferentiated carcinomas. Immunoreactivity for dysadherin, localized at cell-cell boundaries, was detected in 39 of the 51 papillary carcinomas and all 31 undifferentiated carcinomas but not in the follicular carcinomas or normal thyroid tissue controls. Dysadherin expression was significantly higher in undifferentiated carcinoma than in papillary carcinoma and follicular carcinoma and showed significant negative correlation with E-cadherin expression. The degree of dysadherin expression was significantly associated with the prognosis, occurrence of secondary undifferentiated carcinomas, size of the primary tumor, and metastasis to the regional lymph nodes and lungs. In conclusion, a process involving increased dysadherin expression may lead to an adverse clinical outcome.
去黏附素是一种与癌症相关的细胞膜糖蛋白。其cDNA编码178个氨基酸,包括一个推定的信号序列、一个潜在的O-糖基化细胞外结构域、一个单一的跨膜结构域和一个短的细胞质尾巴。去黏附素被认为通过转录后机制下调上皮细胞中细胞间黏附的主要介质E-钙黏蛋白的表达,并促进癌细胞的转移。为了评估甲状腺癌中去黏附素表达与E-钙黏蛋白表达之间的关联,对51例乳头状癌、10例滤泡状癌和31例未分化癌进行了去黏附素和E-钙黏蛋白的免疫染色。去黏附素的免疫反应性定位于细胞间边界,在51例乳头状癌中的39例以及所有31例未分化癌中检测到,但在滤泡状癌或正常甲状腺组织对照中未检测到。去黏附素在未分化癌中的表达明显高于乳头状癌和滤泡状癌,并且与E-钙黏蛋白表达呈显著负相关。去黏附素的表达程度与预后、继发性未分化癌的发生、原发肿瘤的大小以及区域淋巴结和肺转移显著相关。总之,去黏附素表达增加的过程可能导致不良的临床结果。