Glucocorticoid receptor expression in 20 solid tumor types using immunohistochemistry assay

Thaddeus S Block, Tiffany I Murphy, Pamela N Munster, Dat P Nguyen, Frank J Lynch, Thaddeus S Block, Tiffany I Murphy, Pamela N Munster, Dat P Nguyen, Frank J Lynch

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: A validated IHC assay revealed GR immunoreactivity in all solid tumor types studied and allowed for standardized comparison of reactivity among the different malignancies.

Impact: Baseline expression levels of GR may be a useful biomarker when pharmaceutically targeting GR in research or clinical setting.

Keywords: glucocorticoid receptor expression; immunohistochemistry; solid tumors.

Conflict of interest statement

Disclosure TSB and DPN are employees of Corcept Therapeutics, Menlo Park, CA, USA. Corcept Therapeutics sponsored the research reported here. TIM and FJL are employees of QualTek Molecular Laboratories, contracted to perform the assays. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Representative micrographs of immunohistochemical GR staining in various tumor types showing variations in levels of staining. Note: Tumors with ≥10% GR staining at the following intensities: 0, 1+, 2+, and 3+. Abbreviation: GR, glucocorticoid receptor; TNBC, triple-negative breast cancer.
Figure 2
Figure 2
Glucocorticoid receptor positivity by mean H-score. Note: The H-score was calculated as [(% at 0)×0]+[(% at 1+)×1]+[(% at 2+)×2]+[(% at 3+)×3]; thus, the H-score produces a continuous variable that ranges from 0 to 300. Abbreviation: TNBC, triple-negative breast cancer.
Figure 3
Figure 3
Average percent staining of glucocorticoid receptor at various intensities. Note: Bars show the distribution of average percent staining across the 0, 1+, 2+, and 3+ categories. Abbreviation: TNBC, triple-negative breast cancer.

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