Block Thaddeus S, Murphy Tiffany I, Munster Pamela N, Nguyen Dat P, Lynch Frank J
Corcept Therapeutics, Inc, Menlo Park, CA; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA.
QualTek Molecular Laboratories, Newtown, PA.
Cancer Manag Res. 2017 Mar 6;9:65-72. doi: 10.2147/CMAR.S124475. eCollection 2017.
Glucocorticoid receptor (GR) activity plays a role in many aspects of human physiology and may play a crucial role in chemotherapy resistance in a wide variety of solid tumors. A novel immunohistochemistry (IHC) based assay has been previously developed and validated in order to assess GR immunoreactivity in triple-negative breast cancer. The current study investigates the standardized use of this validated assay to assess GR expression in a broad range of solid tumor malignancies.
Archived formalin-fixed paraffin-embedded tumor bank samples (n=236) from 20 different solid tumor types were analyzed immunohistochemically. Nuclear staining was reported based on the H-score method using differential intensity scores (0, 1+, 2+, or 3+) with the percent stained (out of at least 100 carcinoma cells) recorded at each intensity.
GR was expressed in all tumor types that had been evaluated. Renal cell carcinoma, sarcoma, cervical cancer, and melanoma were those with the highest mean H-scores, indicating high levels of GR expression. Colon, endometrial, and gastric cancers had lower GR staining percentages and intensities, resulting in the lowest mean H-scores.
A validated IHC assay revealed GR immunoreactivity in all solid tumor types studied and allowed for standardized comparison of reactivity among the different malignancies.
Baseline expression levels of GR may be a useful biomarker when pharmaceutically targeting GR in research or clinical setting.
糖皮质激素受体(GR)活性在人类生理学的许多方面发挥作用,并且可能在多种实体瘤的化疗耐药性中起关键作用。此前已开发并验证了一种基于免疫组织化学(IHC)的新检测方法,用于评估三阴性乳腺癌中的GR免疫反应性。本研究调查了这种经过验证的检测方法在评估多种实体瘤恶性肿瘤中GR表达的标准化应用。
对来自20种不同实体瘤类型的存档福尔马林固定石蜡包埋肿瘤库样本(n = 236)进行免疫组织化学分析。核染色根据H评分法报告,使用差异强度评分(0、1+、2+或3+),并记录每种强度下染色的百分比(至少100个癌细胞中)。
在所评估的所有肿瘤类型中均检测到GR表达。肾细胞癌、肉瘤、宫颈癌和黑色素瘤的平均H评分最高,表明GR表达水平高。结肠癌、子宫内膜癌和胃癌的GR染色百分比和强度较低,导致平均H评分最低。
一种经过验证的IHC检测方法显示在所研究的所有实体瘤类型中均存在GR免疫反应性,并允许对不同恶性肿瘤之间的反应性进行标准化比较。
在研究或临床环境中对GR进行药物靶向治疗时,GR的基线表达水平可能是一种有用的生物标志物。