Department of Pathology, Rhode Island Hospital, and Alpert Medical School of Brown University, Providence, RI 02903, USA.
Hum Pathol. 2011 Nov;42(11):1684-92. doi: 10.1016/j.humpath.2011.01.014. Epub 2011 Apr 29.
Glucocorticoid receptors mediate the action of steroid hormones in a variety of tissues, including the kidney. Our goal was to determine the expression pattern and prognostic significance of glucocorticoid receptor in renal cell neoplasms. Paraffin-embedded microarrays from 200 patients with RCNs including 147 clear cell renal cell carcinomas, 23 papillary, 16 chromophobe renal cell carcinoma, and 14 oncocytomas were analyzed for glucocorticoid receptor expression by immunohistochemistry. Glucocorticoid receptor expression was also quantitated by real-time reverse transcriptase polymerase chain reaction in 45 cases (33 clear cell renal cell carcinomas, 5 chromophobe renal cell carcinomas, and 3 oncocytomas). Strong nuclear glucocorticoid receptor expression was present in normal glomeruli and in the proximal convoluted tubules. Nuclear glucocorticoid receptor expression was found in most clear cell renal cell carcinomas (66%), in 26% of papillary renal cell carcinomas, and in only 6% of chromophobe renal cell carcinomas and 14% of oncocytoma (P < .005). Within the clear cell renal cell carcinoma group, most positive cases (87%) demonstrated strong immunoreactivity (2+ and 3+), whereas only 1 papillary renal cell carcinoma, 1 chromophobe renal cell carcinoma, and none of the oncocytomas showed strong expression. Glucocorticoid receptor α messenger RNA expression was significantly higher in clear cell renal cell carcinoma than in chromophobe renal cell carcinoma, oncocytoma, or in the normal kidney. Significantly more frequent glucocorticoid receptor expression was associated with tumors of low nuclear grade (Fuhrman grade 1 and 2) and low stage (stages 1 and 2; P = .0068 and P = .0002). Survival analysis revealed a significant direct correlation between glucocorticoid receptor expression and overall survival in clear cell renal cell carcinoma (P = .01). In summary, strong glucocorticoid receptor expression was most commonly seen in clear cell renal cell carcinoma and only rarely seen in other subtypes. The glucocorticoid receptor expression pattern in RCNs seems to reflect the histogenetic origin of clear cell renal cell carcinoma from the proximal nephron. Finally, glucocorticoid receptor expression proved to be a marker of less aggressive behavior in clear cell renal cell carcinoma.
糖皮质激素受体介导类固醇激素在多种组织中的作用，包括肾脏。我们的目标是确定糖皮质激素受体在肾细胞肿瘤中的表达模式和预后意义。对 200 例肾细胞肿瘤患者的石蜡包埋微阵列进行了分析，包括 147 例透明细胞肾细胞癌、23 例乳头状肾细胞癌、16 例嫌色细胞肾细胞癌和 14 例嗜酸细胞瘤，通过免疫组织化学法检测糖皮质激素受体的表达。在 45 例病例（33 例透明细胞肾细胞癌、5 例嫌色细胞肾细胞癌和 3 例嗜酸细胞瘤）中，通过实时逆转录聚合酶链反应定量检测糖皮质激素受体的表达。正常肾小球和近端曲管中存在强核糖皮质激素受体表达。在大多数透明细胞肾细胞癌（66%）中发现核糖皮质激素受体表达，在 26%的乳头状肾细胞癌中发现，在只有 6%的嫌色细胞肾细胞癌和 14%的嗜酸细胞瘤中发现（P<0.005）。在透明细胞肾细胞癌组中，大多数阳性病例（87%）表现出强免疫反应（2+和 3+），而只有 1 例乳头状肾细胞癌、1 例嫌色细胞肾细胞癌和 1 例嗜酸细胞瘤没有表现出强表达。糖皮质激素受体α信使 RNA 表达在透明细胞肾细胞癌中明显高于嫌色细胞肾细胞癌、嗜酸细胞瘤或正常肾脏。糖皮质激素受体表达频率更高与核分级较低（Fuhrman 分级 1 和 2）和分期较低（分期 1 和 2）的肿瘤相关（P=0.0068 和 P=0.0002）。生存分析显示，在透明细胞肾细胞癌中，糖皮质激素受体表达与总生存率之间存在显著的直接相关性（P=0.01）。总之，强糖皮质激素受体表达最常见于透明细胞肾细胞癌，而其他亚型则很少见。肾细胞肿瘤中糖皮质激素受体的表达模式似乎反映了透明细胞肾细胞癌从近端肾单位的组织发生起源。最后，糖皮质激素受体表达被证明是透明细胞肾细胞癌侵袭性行为的标志物。
