Department of Visceral Surgery, Jean Bernard Hospital, University Hospital Center (CHU) of Poitiers, Poitiers, France.
Thyroid. 2011 Oct;21(10):1057-66. doi: 10.1089/thy.2011.0041. Epub 2011 Aug 29.
Gap junctions are membrane structures composed of connexins (Cx) that allow diffusion of small molecules between cells. They are involved in tissue homeostasis, and various organ dysfunctions have been associated with gap junction defects. To verify their possible involvement in thyroid pathologies, the expression of connexin43 (Cx43), the major Cx in the human thyroid, was evaluated in a variety of diseases including cancer.
There were 122 samples from various thyroid pathologies that were collected to analyze the presence of Cx43 by immunofluorescence. Through confocal microscopy, different patterns of Cx43 localization were identified as normal (membrane) or abnormal (cytoplasmic or lack of detection). The analysis of Cx43 expression was further performed by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry in a subset of 25 papillary carcinomas and compared with nontumoral thyroid tissues.
The presence of Cx43 was commonly altered in thyroid cancer, as abnormal Cx43 staining was detected in 94.1% of cancer, 47.4% of adenomas, 45.7% of multinodular goiter, 16.7% of Graves' disease, and 25% of thyroiditis. In papillary carcinoma samples, the deregulation of Cx43 expression was mostly the consequence of a decrease of Cx43 mRNA (68% of cases) when compared with normal tissue. When Cx43 mRNA was not downregulated (32% of cases), both loss of membrane staining and aberrant cytoplasmic distribution of the protein were observed.
These results show that aberrations of Cx43 expression are associated with thyroid papillary carcinoma.
间隙连接是由连接蛋白 (Cx) 组成的膜结构，允许小分子在细胞间扩散。它们参与组织稳态，各种器官功能障碍与间隙连接缺陷有关。为了验证它们在甲状腺疾病中的可能参与，评估了主要连接蛋白 Cx43 在包括癌症在内的各种疾病中的表达。
从各种甲状腺病变中收集了 122 个样本，通过免疫荧光法分析 Cx43 的存在。通过共聚焦显微镜，确定了不同的 Cx43 定位模式，分别为正常（膜）或异常（细胞质或检测不到）。在 25 例甲状腺乳头状癌的亚组中，通过定量逆转录-聚合酶链反应和免疫组织化学进一步分析 Cx43 的表达，并与非肿瘤性甲状腺组织进行比较。
在甲状腺癌中 Cx43 的存在通常发生改变，在 94.1%的癌症、47.4%的腺瘤、45.7%的多结节性甲状腺肿、16.7%的格雷夫斯病和 25%的甲状腺炎中检测到异常 Cx43 染色。在甲状腺乳头状癌样本中，与正常组织相比，Cx43 表达的失调主要是 Cx43 mRNA 减少的结果（68%的病例）。当 Cx43 mRNA 没有下调时（32%的病例），观察到膜染色的丧失和蛋白的异常细胞质分布。
这些结果表明，Cx43 表达的异常与甲状腺乳头状癌有关。
