Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Int J Gynecol Pathol. 2012 Jul;31(4):352-7. doi: 10.1097/PGP.0b013e3182469583.
Adiponectin is a cytokine secreted by adipocytes, whose plasma levels are decreased in obesity. Adiponectin has insulin-sensitizing, antiatherogenic, and antidiabetogenic effects. It has been shown that adiponectin may also exert antineoplastic activity through suppression of tumor proliferation and neoangiogenesis and through induction of apoptosis. Recently, low adiponectin serum concentration has been found in obesity-related malignancies, including endometrial cancer. In addition, the expression of adiponectin receptors (AdipoR1 and AdipoR2) has been documented in several human cancer tissues, but the expression has previously not been assessed in human endometrial cancer tissues. In this study, we analyzed the immunohistochemical expression of AdipoR1 and AdipoR2 in a series of surgically resected human endometrioid adenocarcinoma tissues from a total of 141 cases. Decreased AdipoR1 or AdipoR2 expression was significantly associated with histological higher grade (P=0.0026 and 0.0004, respectively). Decreased expression of AdipoR1 was associated with myometrial invasion and lymph node metastasis of endometrioid adenocarcinoma (P=0.0039 and P=0.0069, respectively). AdipoR1 and AdipoR2 immunoexpression was significantly associated with the expression of the progesterone receptor, although it was not significantly correlated with the expression of the estrogen receptor, Ki-67 or p53. Our present study raises the possibility that decreased expression of adiponectin receptors is implicated in the development, invasion, and metastasis of human endometrioid adenocarcinoma. Our findings, moreover, indicate that adiponectin receptors could be considered as therapeutic targets for endometrioid adenocarcinoma. In adiponectin receptor-positive endometrioid adenocarcinoma, we think adiponectin-based anticancer therapy is useful; however, in histological high-grade endometrioid adenocarcinoma, in which the expression levels of adiponectin receptors are relatively low, adiponectin therapy supported by adiponectin receptor induction is needed.
脂联素是一种由脂肪细胞分泌的细胞因子，其在肥胖症患者的血浆水平降低。脂联素具有胰岛素增敏、抗动脉粥样硬化和抗糖尿病作用。已经表明，脂联素还可以通过抑制肿瘤增殖和新生血管形成以及诱导细胞凋亡来发挥抗肿瘤活性。最近，在肥胖相关的恶性肿瘤中，包括子宫内膜癌，发现脂联素血清浓度较低。此外，在几种人类癌症组织中已经记录了脂联素受体（AdipoR1 和 AdipoR2）的表达，但以前尚未在人类子宫内膜癌组织中评估其表达。在这项研究中，我们分析了总共 141 例手术切除的人类子宫内膜样腺癌组织中 AdipoR1 和 AdipoR2 的免疫组织化学表达。AdipoR1 或 AdipoR2 表达降低与组织学高分级显著相关（分别为 P=0.0026 和 0.0004）。AdipoR1 表达降低与子宫内膜样腺癌的子宫肌层浸润和淋巴结转移相关（分别为 P=0.0039 和 P=0.0069）。AdipoR1 和 AdipoR2 的免疫表达与孕激素受体的表达显著相关，尽管与雌激素受体、Ki-67 或 p53 的表达无显著相关性。本研究提出了这样一种可能性，即脂联素受体的表达降低可能与人类子宫内膜样腺癌的发生、浸润和转移有关。此外，我们的研究结果表明，脂联素受体可以被认为是子宫内膜样腺癌的治疗靶点。在脂联素受体阳性的子宫内膜样腺癌中，我们认为基于脂联素的抗癌治疗是有用的；然而，在组织学高级别的子宫内膜样腺癌中，脂联素受体的表达水平相对较低，需要通过诱导脂联素受体来支持脂联素治疗。
