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Article

Glucocorticoid Receptor (GR) Expression in Human Tumors: A Tissue Microarray Study on More than 14,000 Tumors

by
Maria Christina Tsourlakis
1,
Simon Kind
1,
Sebastian Dwertmann Rico
1,
Sören Weidemann
1,
Katharina Möller
1,
Ria Schlichter
1,
Martina Kluth
1,
Claudia Hube-Magg
1,
Christian Bernreuther
1,
Guido Sauter
1,
Andreas H. Marx
2,
Ronald Simon
1,*,
Ahmed Abdulwahab Bawahab
3,
Florian Lutz
1,
Viktor Reiswich
1,
Davin Dum
1,
Stefan Steurer
1,
Eike Burandt
1,
Till S. Clauditz
1,
Till Krech
1,4,
Christoph Fraune
1,4,
Seyma Büyücek
1,
Neele Heckmann
1,
Natalia Gorbokon
1,
Maximilian Lennartz
1,
Sarah Minner
1 and
Florian Viehweger
1add Show full author list remove Hide full author list
1
Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
2
Department of Pathology, Academic Hospital Fuerth, 90766 Fuerth, Germany
3
Department of Basic Medical Sciences, Pathology Division, College of Medicine, University of Jeddah, Jeddah 23890, Saudi Arabia
4
Institute of Pathology, Clinical Center Osnabrueck, 49076 Osnabrueck, Germany
*
Author to whom correspondence should be addressed.
Biomedicines 2025, 13(7), 1683; https://doi.org/10.3390/biomedicines13071683
Submission received: 23 April 2025 / Revised: 2 July 2025 / Accepted: 2 July 2025 / Published: 9 July 2025
(This article belongs to the Section Cancer Biology and Oncology)
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Versions Notes

Abstract

Background: The glucocorticoid receptor (GR) regulates the transcription of thousands of genes. In cancer, both oncogenic and tumor suppressive roles of GR have been proposed. Methods: A tissue microarray containing 18,527 samples from 147 tumor (sub-)types and 608 samples from 76 normal tissue types was analyzed for GR expression by immunohistochemistry. Results: GR positivity was found in 76.4% of 14,349 interpretable cancers, including 18.5% with weak, 19.6% with moderate, and 38.3% with strong positivity. GR positivity appeared in all 147 tumor types, with at least one strongly positive tumor in 136 types. Of out tumor entities, 77 of the 147 showed GR positivity in 100% of the cases analyzed. Only six tumor types had less than 50% GR-positive cases, including adenomas with low-/high-grade dysplasia (32.5%/21.7%), adenocarcinomas (17%) and neuroendocrine carcinomas (45.5%) of the colorectum, endometrial carcinomas (25.6%), and rhabdoid tumors (25%). Reduced GR staining was associated with grade progression in pTa (p < 0.0001) and with nodal metastasis in pT2-4 (p = 0.0051) urothelial bladder carcinoma, advanced pT stage (p = 0.0006) in breast carcinomas of no special type (NST), and high grade (p = 0.0066), advanced pT stage (p < 0.0001), and distant metastasis (p = 0.0081) in clear cell renal cell carcinoma. GR expression was unrelated to clinico-pathological parameters in gastric, pancreatic, and colorectal adenocarcinoma, and in serous high-grade carcinoma of the ovary. Conclusions: GR expression is frequent across all cancer types. Associations between reduced GR expression and unfavorable tumor features in certain cancers suggest that the functional importance of GR-regulated genes in cancer progression depends on the cell of tumor origin.

1. Introduction

The glucocorticoid receptor (GR) is a multidomain nuclear protein which is coded by the NR3C1 (nuclear receptor subfamily 3, group C, member 1) gene at 5q31 [1,2]. GR is one of the members of the nuclear receptor (NR) superfamily subgroup 3 which also contains the androgen receptor (AR), mineralocorticoid receptor (MR), progesterone receptor (PR) and the two estrogen receptors (ERα and ERβ) (reviewed in [3]). GR is the most relevant receptor protein for cortisol and other glucocorticoids [4]. Depending on ligand binding and the recruitment of context-specific transcriptional coregulators, GR modulates either the activation or repression of the transcription of a broad range of different genes involved in development, metabolism, stress, and inflammatory responses (reviewed in [5,6]). GR and glucocorticoids have a critical impact on diverse physiological processes (reviewed in [5]) and are integral to the treatment of hematological malignancies due to their potent anti-inflammatory and lympholytic effects [7].
Multiple studies have provided evidence that GR expression plays a complex role in tumorigenesis which goes way beyond its effects on the immune system. Both oncogenic and tumor-suppressive roles of GR have been found depending on tumor type and on specific tumor characteristics (reviewed in [8]). For example, in breast cancer, GR expression was linked to favorable patient outcomes in ER-positive cancer [9,10] but related to shorter breast cancer specific survival, poor prognosis, resistance to chemotherapy, and metastasis in ER-negative cancer [9,11,12]. In prostate cancer, GR activation inhibited tumor angiogenesis [13] and reduced proliferation in primary hormone-sensitive prostate cancer cell lines [14], while GR signaling facilitated resistance to anti-androgen therapies in advanced prostate cancer [15,16]. Most of the clinical interest in GR expression in cancer comes from its potential as a druggable target, although the effects of glucocorticoid treatment in solid cancers are complex and sometimes controversial. For example, GR antagonists have shown promise in the therapy of triple negative breast cancer [12], but the effects of glucocorticoid therapies in hormone receptor positive breast cancer can vary with its subtype and molecular profile [17]. In prostate cancer, GR overexpression has been shown to constitute a mechanism for androgen resistance [15,18]. In concordance with these findings, preclinical studies provided evidence that inhibition of the GR pathway leads to re-sensitization to antiandrogen therapy and chemotherapeutics like docetaxel [16,19].
Despite of its potential importance, data on GR protein expression in tumors are still sparse and considerably variable. For example, the reported range of GR positivity found in studies using immunohistochemistry (IHC) for GR detection ranged from 0 to 100% in breast carcinoma [11,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36], 20–100% in prostate carcinoma [14,24,37,38,39], 27–100% in ductal adenocarcinoma of the pancreas [24,40,41,42], 45–94% in non-small cell lung cancer [43,44,45,46,47], and 0–48% in colorectal adenocarcinoma [41,48]. Varying positivity rates in different IHC studies are likely due to the use of different antibodies, staining protocols, and criteria for defining positivity.
To overcome such shortcomings, a comprehensive and highly standardized study using one highly validated antibody and immunohistochemistry protocol to analyze many tumors from different tumor entities is of interest. Accordingly, GR expression was analyzed in more than 14,000 tumor tissue samples from 147 different tumor types and subtypes as well as 76 different non-neoplastic tissue types by IHC in a tissue microarray (TMA) format in this study.

2. Materials and Methods

2.1. Tissue Microarrays (TMAs)

Our normal TMA was composed of 8 samples from 8 different donors of 76 different normal tissue types (608 samples on one slide). The cancer TMAs included a total of 18,527 primary tumors from 147 different tumor types and subtypes. Detailed histopathological data were available for invasive breast carcinomas of no special type (n = 1680), urothelial carcinomas of the bladder (n = 2434), colorectal adenocarcinomas (n = 2351), endometrioid endometrial carcinomas (n = 182), clear cell renal cell carcinomas (n = 1224), papillary renal cell carcinomas (n = 310), serous high-grade ovarian carcinomas (n = 369), ductal adenocarcinomas of the pancreas (n = 598), papillary thyroid carcinomas (n = 382), gastric adenocarcinomas (n = 327), and germ cell tumors of the testis (n = 565). Clinical follow up data were accessible for 717 patients with invasive breast carcinoma of no special type (NST) patients with a median follow-up time of 50 months. The composition of normal and cancer TMAs is described in the Section 3. All samples were from the archives of the Institute of Pathology, University Hospital of Hamburg, Germany, the Institute of Pathology, Clinical Center Osnabrueck, Germany, and the Department of Pathology, Academic Hospital Fuerth, Germany. The samples were collected from patients who underwent surgery for tumor resection between 1994 and 2020. Data on patient gender were available for 10,398 tumor samples with interpretable GR data and included 4537 males and 5861 females. Tissues were fixed in 4% buffered formalin and then embedded in paraffin. The TMA manufacturing process was described previously in detail [49]. In brief, one tissue spot (diameter: 0.6 mm) per tissue sample (one sample per patient) patient was used. The use of archived remnants of diagnostic tissues for TMA manufacturing, their analysis for research purposes, and the use of patient data were carried out according to local laws (HmbKHG, §12) and our analysis was approved by the local ethics committee (Ethics commission Hamburg, WF-049/09). All work has been carried out in compliance with the Helsinki Declaration.

2.2. Immunohistochemistry (IHC)

Freshly cut TMA sections were immunostained on one day and in one experiment. Slides were deparaffinized with xylol, rehydrated through a graded alcohol series, and exposed to heat-induced antigen retrieval for 5 min in an autoclave at 121 °C in pH 7.8 Tris-EDTA-Citrat (TEC) buffer. Endogenous peroxidase activity was blocked with Dako REAL Peroxidase-Blocking Solution (Agilent Technologies, Santa Clara, CA, USA; #S2023) for 10 min. A primary antibody specific for the Glucocorticoid receptor (GR) (HMV304, rabbit recombinant monoclonal, ardoci GmbH, Hamburg, Germany) was applied at 37 °C for 60 min at a dilution of 1:150. For the purpose of antibody validation, the normal tissue TMA was also analyzed using the rabbit recombinant monoclonal antibody EPR19621 (Abcam, Cambridge, MA, USA, #ab183127) at a dilution of 1:600 and an otherwise identical protocol. The bound antibody was then visualized using the Dako REAL EnVision Detection System Peroxidase/DAB+, Rabbit/Mouse kit (Agilent Technologies, Santa Clara, CA, USA; #K5007) according to the manufacturer’s directions. The sections were counterstained with hemalaun. For tumor tissues, all tumor cells present in a given tissue spot were scored. The percentage of positive neoplastic cells was estimated, and the staining intensity was semi-quantitatively recorded (0, 1+, 2+, 3+). For statistical analyses, the staining results were categorized into four groups. Tumors without any staining were considered negative. Tumors with 1+ staining intensity in ≤70% of tumor cells or 2+ intensity in ≤30% of tumor cells were considered weakly positive. Tumors with 1+ staining intensity in >70% of tumor cells, 2+ intensity in 31–70%, or 3+ intensity in ≤30% of tumor cells were considered moderately positive. Tumors with 2+ intensity in >70% or 3+ intensity in >30% of tumor cells were considered strongly positive.

2.3. Statistics

Statistical calculations were performed with JMP17® software (SAS®, Cary, NC, USA). Levene’s test for normality and homogeneity was used to assess similar variances before statistical analysis. Contingency tables and the chi2-test were performed to search for associations between GR immunostaining and tumor phenotype. The Log-Rank test was applied to detect significant differences between groups. A p-value of ≤0.05 was defined as significant.

3. Results

3.1. Technical Issues

A total of 14,349 (77.4%) of the 18,527 tumor samples collected were interpretable in our TMA analysis. The non-interpretable samples demonstrated a lack of unequivocal tumor cells or a lack of entire tissue spots. A sufficient number of samples (≥4) of each normal tissue type was evaluable.

3.2. Glucocorticoid Receptor Immunostaining in Normal Tissues

GR immunostaining was always nuclear and seen in almost all cell types of all organs. Cell types with either reduced or absent GR staining included the upper cell layers of the non-keratinizing squamous epithelium and of the urothelium, corpuscles of Hassall’s from the thymus, glandular cells from the stomach, crypt base epithelial cells from the appendix and the colorectum, glandular cells from the endometrium in the secretion phase, cells from the spermiogenesis, granulosa cells from the ovary, adrenocortical cells, and trophoblastic cells from the mature (and not the first trimenon) placenta. Tissues with at least moderate-to-strong GR staining of all cell types or cell types with at least moderate GR staining included the prostate, seminal vesicle, epididymis, Sertoli and Leydig cells from the testis, fallopian tube, endocervix, stroma cells from the endometrium, myometrium, theca interna, corpus luteum, and stromal cells from the ovary, breast, basal respiratory epithelium, skeletal muscle cells, smooth muscle cells, kidney, gallbladder, pancreas (stronger staining in islet cells than in acinar cells), salivary glands, thyroid, decidua cells and endometrium of the pregnant uterus, cells of the aortic wall, medullary cells of the adrenal gland, parathyroid, hematopoietic and lymphoid tissues, lung, hypophysis, and neurons from the cerebrum. Examples of GR staining in normal tissues are shown in Figure 1. All these staining patterns were observed by using both HMV304 and EPR19621 (Supplementary Figure S1).

3.3. Glucocorticoid Receptor Immunostaining in Neoplastic Tissues

GR staining was always nuclear in the tumors. GR positivity was found in 76.4% of the 14,349 interpretable cancers, including 18.5% with weak, 19.6% with moderate, and 38.3% with strong positivity. GR positivity of at least a fraction of tumors was found in all 147 tumor types analyzed and at least one strongly GR-positive tumor was found in 136 tumor types (Table 1).
Of our tumor entities, 77 of the 147 showed GR positivity of variable intensity in all analyzed cases. A further 43 tumor entities showed GR positivity in 80–99.9% of cases. And 21 tumor entities had a GR positivity rate between 50 and 80%, including urothelial carcinoma as well as gastric and esophageal adenocarcinoma. Only six tumor types had less than 50% GR-positive samples. These included adenomas with low- and high-grade dysplasia (32.5% and 21.7%), adenocarcinomas (17%) and neuroendocrine carcinomas (45.5%) of the colorectum, and endometrioid endometrial carcinomas (25.6%), as well as rhabdoid tumors (25%). Representative images of GR-positive and -negative tumors are shown in Figure 2.
A ranking of tumor categories according to the rate of GR positivity is given in Figure 3.
Reduced GR staining was significantly associated with adverse histopathological and clinical features in multiple tumor types (Table 2).
Low GR expression was linked to grade progression in pTa (p < 0.0001) and to nodal metastasis in pT2-4 (p = 0.0051) urothelial carcinoma of the urinary bladder and advanced pT stage (p = 0.0006) in breast carcinomas of no special type (NST), as well as to high-grade (p = 0.0066), advanced pT stage (p < 0.0001), and distant metastasis (p = 0.0081) in clear cell renal cell carcinoma. GR expression was unrelated to clinico-pathological parameters in gastric, pancreatic and colorectal adenocarcinoma, as well as in serous high-grade carcinoma of the ovary.

4. Discussion

Our successful evaluation of more than 14,000 samples from 147 different tumor types and subtypes provides a comprehensive overview on the prevalence of GR expression in cancer. That GR expression was observed in all 147 cancer entities and that only six of them showed a positivity rate below 50% identifies GR expression as a common feature of cancers cells. In general, this finding is in line with the previous literature on GR immunostaining in cancer (summarized in Supplementary Figure S2 [20,21,22,24,26,27,29,30,31,34,35,36,40,46,47,50,51,52,53,54,55,56,57,58] although published data were controversial for several entities. The particularly low rate of GR positivity in colorectal cancer (17.1%, including 14.5% with low level positivity) is in agreement with an earlier study reporting negative GR immunostaining in all 35 analyzed colorectal adenocarcinomas [41]. The frequent high-level GR positivity in the vast majority of cancer types indicates limited potential for GR IHC as a tool for the distinction of tumor entities. There are, however, two possible applications which may deserve further evaluation. The much higher GR positivity rate in adrenocortical carcinoma (88% of 25 with moderate/strong staining) than in adrenocortical adenoma (15.5% of 45 with moderate/strong staining) suggests that GR IHC could help in the otherwise challenging distinction of benign from malignant adrenocortical neoplasms (reviewed in [59]). Based on the very low frequency of colorectal adenocarcinomas with moderate (2.4%) and strong (0.2%) GR positivity, a significant GR positivity by IHC would argue against a colorectal origin of an adenocarcinoma metastasis. Other adenocarcinomas, such as those from the pancreas (84.3%), the gallbladder (77.1%), the stomach (24.4%), the esophagus (36.4%), the lung (92.1%), or the prostate (56.7%) had markedly higher rates of moderate-to-strong GR positivity.
The availability of large tumor cohorts from several frequent cancer types enabled us to evaluate the relationship between GR expression and clinico-pathological parameters of cancer aggressiveness in several tumor types. That reduced GR expression was linked to unfavorable tumor features in breast cancer, clear cell renal cell carcinoma, and in urothelial carcinoma is in line with data from earlier studies [11,25,60,61]. Associations between reduced GR expression and unfavorable tumor features have also been described for adrenocortical carcinomas [50], thymic epithelial tumors [62], ductal adenocarcinoma of the pancreas [42], cervical cancer [56], colorectal adenocarcinomas, and non-small cell lung cancer [45]. Overall, these observations argue for a tumor-suppressive role of GR in these tumor entities. Data from functional studies have supported the tumor suppressive function of GR in some tumor types. Caratti et al. found that deletion of the GR in A549 lung cancer cells enhanced tumor growth of xenografts in mice [63]. Matthews et al. reported an essential role of GR for proper cell cycle progression in HeLa cells and observed mitotic aberrations and tumor formation in mice that were haploinsufficient for GR [64]. Yemelyanov et al. described an inhibition of cell proliferation and a blockage of anchorage-independent growth after lentiviral reconstitution of GR expression in GR-negative LNCaP prostate cancer cells [14]. Alternatively, reduced GR expression in tumors derived from GR expressing normal cells could just reflect tumor cell dedifferentiation paralleling cancer progression. Importantly, low GR expression is not a general feature of poor prognosis in cancer. GR expression was unrelated to clinico-pathological features in multiple tumor entities in this study. Moreover, a strong and independent correlation between high GR expression and poor clinical outcomes was recently found by our group in a cohort of 12,152 prostate cancer samples by using the same IHC assay as in this study (Heckmann et al., submitted). Others have also found a link between high GR expression and unfavorable tumor phenotype in prostate cancer [65] as well as in several other cancer types such as ovarian cancer [51,66], endometrial cancer [57], salivary duct carcinoma [52], malignant melanoma [67], and squamous cell carcinoma of the esophagus [53]. The mechanisms by which GR upregulation was found to increase cancer aggressiveness include promotion of epithelial–mesenchymal transformation by transcriptional repression of insulin receptor substrate 1 in breast cancer cells [68], escape from apoptosis by repression of p38 MAP kinase in cervical cancer cells [69], bypass of androgen receptor blockade in prostate cancer cells [70], and increased glycolytic energy production through the suppression of mitochondrial pyruvate dehydrogenase in liver cancer cells [71].
Glucocorticoids are widely used in cancer patients to reduce the side effects of chemotherapy and radiation and to protect healthy tissue from toxicity. Considering the widespread but variable expression of GR in cancer, it must be assumed that the application of steroids can also directly impact cancer cells and exert clinical effects that may remain clinically unrecognized in the context of severe illness in affected patients. Several studies have indeed demonstrated the direct effects of steroid hormones on tumor cell behavior. The GR agonist dexamethasone induced a gene signature that correlated with shorter survival in The Cancer Genome Atlas glioblastoma dataset [72], enhanced tumor growth and metastasis in breast cancer xenograft mouse models [73], transcriptionally activated TEA domain transcription factor 4, the expression of which correlates with poor survival of patients with breast cancer [74], and favored epithelial–mesenchymal transition, self-renewal potential, and cancer progression in pancreatic ductal adenocarcinoma cell lines [75]. Although GR antagonists are generally explored for their potential to mitigate the pro-tumorigenic effects of glucocorticoids, there is some evidence that also antagonists such as mifepristone may promote tumor progression in specific settings. For example, mifepristone significantly stimulated ovarian cancer cell migration, proliferation, and growth in vivo [76], and promoted testicular Leydig cell tumor progression in transgenic mice [77]. Other studies have demonstrated that GR agonists and antagonists can impact tumor cell responses to chemotherapy in several experimental models of solid tumors. For example, GR agonists induced chemotherapy resistance in lung cancer, prostate cancer, breast cancer and ovarian cancer cells [15,78,79,80,81]. GR antagonists, such as mifepristone or relacorilant could reverse chemotherapy resistance and potentiate chemotherapy-induced apoptosis in triple-negative breast cancer, pancreatic cancer, and ovarian cancer cell lines [12,82].
Given the large scale of our study, particular emphasis was placed on a thorough validation of our assay. The International Working Group for Antibody Validation (IWGAV) has proposed that an acceptable antibody validation for immunohistochemistry on formalin fixed tissues must include either a comparison of IHC findings with a second antibody for the same target or a comparison with another independent method for expression analysis [83]. Because comparison with a method using disaggregated tissue is not well suited in case of ubiquitously expressed proteins, we performed an extensive comparison of antibodies on 76 different categories of normal tissues. These experiments confirmed the specificity of our assay because all staining patterns obtained by HMV304 were confirmed by EPR19621. These included a reduction or loss of GR expression in upper cell layers of non-keratinizing squamous epithelium and of the urothelium, cells of the spermiogenesis, granulosa cells of the ovary, adrenocortical cells, and trophoblastic cells of the mature but not of the first trimenon placenta. It is of note that the use of a very broad range of different tissues (76 different normal tissue categories) for antibody validation increases the likelihood of detecting undesired cross-reactivities because virtually all proteins occurring in normal cells of adult humans are subjected to the validation experiment.

5. Conclusions

Our data provide a comprehensive overview of GR expression in normal and neoplastic human tissues. Significant associations between reduced GR expression and unfavorable tumor features in some but not all tumor types demonstrates that the functional effects of GR expression significantly depend on the tumor cell type. The potential role of GR expression as a predictive marker for both the response to GR-targeted therapies and the side-effects of GR-agonists administered to cancer patients has to be evaluated further.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/biomedicines13071683/s1, Figure S1: IHC validation by comparison of two antibodies; Figure S2: IHC validation by comparison of two antibodies Table S1: List of studies used to generate Supplementary Figure S2.

Author Contributions

Conceptualization, M.C.T., F.V., R.S. (Ronald Simon), M.K. and G.S.; validation, M.C.T., G.S., F.V.; M.C.T., F.V., R.S. (Ronald Simon), M.K. and G.S.; formal analysis, S.K., S.D.R., S.W., K.M., R.S. (Ria Schlichter), C.B., A.H.M., A.A.B., F.L., V.R., D.D., S.S., E.B., T.S.C., T.K., C.F., S.B., N.H., N.G., M.L. and S.M.; resources, S.K., S.D.R., S.W., K.M., R.S. (Ria Schlichter), C.B., A.H.M., A.A.B., F.L., V.R., D.D., S.S., E.B., T.S.C., T.K., C.F., S.B., N.H., N.G., M.L. and S.M.; data curation, M.C.T., M.K., C.H.-M. and R.S. (Ronald Simon) writing—original draft preparation M.C.T., F.V., R.S. (Ronald Simon), M.K. and G.S.; visualization, R.S. (Ronald Simon), M.K. and C.H.-M.; supervision, M.C.T., R.S. (Ronald Simon) and G.S.; project administration, M.C.T., F.V. and G.S.; All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The use of archived remnants of diagnostic tissues for manufacturing of TMAs and their analysis for research purposes as well as patient data analysis has been approved by local laws (HmbKHG, §12) and by the local ethics committee (Ethics commission Hamburg, WF-049/09). All work has been carried out in compliance with the Helsinki Declaration.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study (HmbKHG, §12).

Data Availability Statement

All data generated or analyzed during this study are included in this published article.

Acknowledgments

We are grateful to Melanie Steurer, Laura Behm, Inge Brandt, and Sünje Seekamp for excellent technical assistance.

Conflicts of Interest

The GR antibody, clone HMV304 was provided by ardoci GmbH, Hamburg, Germany (owned by a family member of GS).

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Biomedicines 13 01683 g001
Figure 1. GR immunostaining of normal tissues. The panels show a variable but usually strong nuclear GR in all cell types of the breast (A), fallopian tube (B), prostate (C), skeletal muscle (D), lung (E), kidney (F), and the pancreas, (G) while GR staining is markedly reduced in cells of spermiogenesis in the testis (see arrowheads in (H)).
Figure 1. GR immunostaining of normal tissues. The panels show a variable but usually strong nuclear GR in all cell types of the breast (A), fallopian tube (B), prostate (C), skeletal muscle (D), lung (E), kidney (F), and the pancreas, (G) while GR staining is markedly reduced in cells of spermiogenesis in the testis (see arrowheads in (H)).
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Figure 2. GR immunostaining in cancer. The panels show a moderate-to-strong GR positivity in tumor cells from squamous cell carcinoma of the cervix (A), adenocarcinoma of the lung (B), ductal adenocarcinoma of the pancreas (C), prostatic adenocarcinoma (D), gastric adenocarcinoma (E), and adrenocortical carcinoma (F). GR staining is lacking in tumor cells from a colorectal adenocarcinoma (G) and an adrenocortical adenoma (H) while distinct GR staining occurs in stromal cells.
Figure 2. GR immunostaining in cancer. The panels show a moderate-to-strong GR positivity in tumor cells from squamous cell carcinoma of the cervix (A), adenocarcinoma of the lung (B), ductal adenocarcinoma of the pancreas (C), prostatic adenocarcinoma (D), gastric adenocarcinoma (E), and adrenocortical carcinoma (F). GR staining is lacking in tumor cells from a colorectal adenocarcinoma (G) and an adrenocortical adenoma (H) while distinct GR staining occurs in stromal cells.
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Figure 3. Ranking order of GR immunostaining in tumors. Both the overall percentage of positive cases (gray bars) and the fraction of strongly positive cases (black bars) are shown.
Figure 3. Ranking order of GR immunostaining in tumors. Both the overall percentage of positive cases (gray bars) and the fraction of strongly positive cases (black bars) are shown.
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Table 1. GR immunostaining in human tumors.
Table 1. GR immunostaining in human tumors.
GR Immunostaining
Tumor CategoryTumor EntityOn TMA (n)Analyzable (n)Negative (%)Weak (%)Moderate (%)Strong (%)
Tumors of the skinBasal cell carcinoma of the skin89620.032.338.729.0
Benign nevus29200.00.00.0100.0
Squamous cell carcinoma of the skin1451021.02.911.884.3
Malignant melanoma65480.08.38.383.3
Malignant melanoma lymph node metastasis86724.213.918.163.9
Merkel cell carcinoma210.00.00.0100.0
Tumors of the head and neckSquamous cell carcinoma of the larynx109790.02.58.988.6
Squamous cell carcinoma of the pharynx60560.05.412.582.1
Oral squamous cell carcinoma (floor of the mouth)1301110.01.814.483.8
Pleomorphic adenoma of the parotid gland50300.00.010.090.0
Warthin tumor of the parotid gland104630.06.342.950.8
Adenocarcinoma, NOS (Papillary Cystadenocarcinoma)1440.00.050.050.0
Salivary duct carcinoma1530.00.033.366.7
Acinic cell carcinoma of the salivary gland181412.40.07.390.2
Adenocarcinoma NOS of the salivary gland1092222.79.127.340.9
Adenoid cystic carcinoma of the salivary gland180140.028.642.928.6
Basal cell adenocarcinoma of the salivary gland25110.09.136.454.5
Basal cell adenoma of the salivary gland101240.00.08.391.7
Epithelial-myoepithelial carcinoma of the salivary gland531513.30.033.353.3
Mucoepidermoid carcinoma of the salivary gland3431220.818.915.664.8
Myoepithelial carcinoma of the salivary gland2180.00.012.587.5
Myoepithelioma of the salivary gland1140.00.00.0100.0
Oncocytic carcinoma of the salivary gland1220.00.00.0100.0
Pleomorphic adenoma of the salivary gland53170.00.00.0100.0
Tumors of the lung, pleura, and thymusAdenocarcinoma of the lung1961511.36.625.266.9
Squamous cell carcinoma of the lung80590.06.850.842.4
Mesothelioma, epithelioid40320.06.328.165.6
Mesothelioma, biphasic29220.09.122.768.2
Thymoma29220.00.027.372.7
Lung, neuroendocrine tumor (NET)29210.014.30.085.7
Tumors of the female genital tractSquamous cell carcinoma of the vagina78504.06.014.076.0
Squamous cell carcinoma of the vulva1571200.01.715.083.3
Squamous cell carcinoma of the cervix1361130.99.731.058.4
Adenocarcinoma of the cervix23219.519.033.338.1
Endometrioid endometrial carcinoma33828974.418.75.21.7
Endometrial serous carcinoma866530.833.824.610.8
Carcinosarcoma of the uterus575010.032.044.014.0
Endometrial carcinoma, high grade, G3131346.223.130.80.0
Endometrial clear cell carcinoma9825.037.537.50.0
Endometrioid carcinoma of the ovary1309644.822.97.325.0
Serous carcinoma of the ovary5804674.721.837.536.0
Mucinous carcinoma of the ovary1017216.715.334.733.3
Clear cell carcinoma of the ovary514131.729.322.017.1
Carcinosarcoma of the ovary473810.531.634.223.7
Granulosa cell tumor of the ovary44380.026.350.023.7
Leydig cell tumor of the ovary440.025.025.050.0
Sertoli cell tumor of the ovary110.0100.00.00.0
Sertoli Leydig cell tumor of the ovary330.00.033.366.7
Steroid cell tumor of the ovary330.033.30.066.7
Brenner tumor41360.027.844.427.8
Tumors of the breastInvasive breast carcinoma of no special type1764148916.431.833.718.1
Lobular carcinoma of the breast36324016.330.032.121.7
Medullary carcinoma of the breast342520.028.024.028.0
Tubular carcinoma of the breast291520.020.033.326.7
Mucinous carcinoma of the breast654526.731.126.715.6
Phyllodes tumor of the breast50400.02.510.087.5
Tumors of the digestive systemAdenomatous polyp, low-grade dysplasia504067.530.02.50.0
Adenomatous polyp, high-grade dysplasia504678.321.70.00.0
Adenocarcinoma of the colorectum2483224283.014.52.40.2
Gastric adenocarcinoma, diffuse type21512948.134.114.03.9
Gastric adenocarcinoma, intestinal type21516044.429.421.35.0
Gastric adenocarcinoma, mixed type625133.331.429.45.9
Adenocarcinoma of the esophagus834429.534.136.40.0
Squamous cell carcinoma of the esophagus76385.37.928.957.9
Squamous cell carcinoma of the anal canal91750.01.316.082.7
Cholangiocarcinoma58484.212.529.254.2
Gallbladder adenocarcinoma51355.717.140.037.1
Gallbladder Klatskin tumor42300.016.733.350.0
Hepatocellular carcinoma3122891.718.029.850.5
Ductal adenocarcinoma of the pancreas6594540.215.443.840.5
Pancreatic/Ampullary adenocarcinoma987723.435.131.210.4
Acinar cell carcinoma of the pancreas18160.06.343.850.0
Gastrointestinal stromal tumor (GIST)62560.01.87.191.1
Appendix, neuroendocrine tumor (NET)25119.19.10.081.8
Colorectal, neuroendocrine tumor (NET)12100.00.010.090.0
Ileum, neuroendocrine tumor (NET)53470.00.017.083.0
Pancreas, neuroendocrine tumor (NET)101890.03.411.285.4
Colorectal, neuroendocrine carcinoma (NEC)141154.527.318.20.0
Ileum, neuroendocrine carcinoma (NEC)8333.30.00.066.7
Gallbladder, neuroendocrine carcinoma (NEC)440.00.075.025.0
Pancreas, neuroendocrine carcinoma (NEC)14110.00.054.545.5
Tumors of the urinary systemNon-invasive papillary urothelial ca., pTa G2 low grade87738.215.16.869.9
Non-invasive papillary urothelial ca., pTa G2 high grade806731.310.411.946.3
Non-invasive papillary urothelial carcinoma, pTa G312610847.218.511.123.1
Urothelial carcinoma, pT2-4 G373544230.513.312.743.4
Squamous cell carcinoma of the bladder22210.00.038.161.9
Small cell neuroendocrine carcinoma of the bladder530.00.066.733.3
Sarcomatoid urothelial carcinoma25185.611.127.855.6
Urothelial carcinoma of the kidney pelvis625337.730.218.913.2
Clear cell renal cell carcinoma128711242.612.518.966.1
Papillary renal cell carcinoma3683072.314.723.559.6
Clear cell (tubulo) papillary renal cell carcinoma26214.819.04.871.4
Chromophobe renal cell carcinoma17014912.838.920.128.2
Oncocytoma2572004.019.530.546.0
Tumors of the male genital organsAdenocarcinoma of the prostate, Gleason 3+383593.450.844.11.7
Adenocarcinoma of the prostate, Gleason 4+480577.043.936.812.3
Adenocarcinoma of the prostate, Gleason 5+5856714.934.331.319.4
Adenocarcinoma of the prostate (recurrence)2581297.024.838.030.2
Seminoma68261438.356.55.00.2
Embryonal carcinoma of the testis544850.047.92.10.0
Leydig cell tumor of the testis31290.00.013.886.2
Sertoli cell tumor of the testis2250.00.00.050.0
Sex cord stromal tumor of the testis110.0100.00.00.0
Spermatocytic tumor of the testis110.00.00.0100.0
Yolk sac tumor534027.570.02.50.0
Teratoma53350.08.68.682.9
Squamous cell carcinoma of the penis92810.00.08.691.4
Tumors of endocrine organsAdenoma of the thyroid gland113890.02.216.980.9
Papillary thyroid carcinoma3913320.35.438.056.3
Follicular thyroid carcinoma1541110.02.713.583.8
Medullary thyroid carcinoma111760.00.017.182.9
Parathyroid gland adenoma43372.72.78.186.5
Anaplastic thyroid carcinoma45380.07.936.855.3
Adrenal cortical adenoma48458.975.613.32.2
Adrenal cortical carcinoma27254.08.028.060.0
Pheochromocytoma51462.215.230.452.2
Tumors of hematopoetic and lymphoid tissuesHodgkin Lymphoma103670.06.011.982.1
Small lymphocytic lymphoma, B-cell type (B-SLL/B-CLL)50480.00.014.685.4
Diffuse large B cell lymphoma (DLBCL)1131120.01.813.484.8
Follicular lymphoma88880.02.313.684.1
T-cell Non Hodgkin lymphoma25240.04.24.291.7
Mantle cell lymphoma18170.00.017.682.4
Marginal zone lymphoma16150.06.70.093.3
Diffuse large B-cell lymphoma (DLBCL) in the testis16150.00.026.773.3
Burkitt lymphoma530.033.333.333.3
Tumors of soft tissue and boneGranular cell tumor23195.35.35.384.2
Leiomyoma50420.026.211.961.9
Leiomyosarcoma94780.010.321.867.9
Liposarcoma96770.05.214.380.5
Malignant peripheral nerve sheath tumor (MPNST)15130.00.015.484.6
Myofibrosarcoma26260.00.07.792.3
Angiosarcoma42310.03.212.983.9
Angiomyolipoma91790.01.310.188.6
Dermatofibrosarcoma protuberans21130.00.07.792.3
Ganglioneuroma14120.00.08.391.7
Kaposi sarcoma850.020.00.080.0
Neurofibroma117980.00.03.196.9
Sarcoma, not otherwise specified (NOS)74631.67.922.268.3
Paraganglioma41390.05.135.959.0
Ewing sarcoma23137.723.146.223.1
Rhabdomyosarcoma770.014.328.657.1
Schwannoma1221060.00.01.998.1
Synovial sarcoma12100.010.020.070.0
Osteosarcoma19140.021.414.364.3
Chondrosarcoma151010.00.030.060.0
Rhabdoid tumor5475.00.025.00.0
Solitary fibrous tumor17170.00.05.994.1
Table 2. GR immunostaining and tumor phenotype.
Table 2. GR immunostaining and tumor phenotype.
Tumor EntityPathological and Molecular Parameters GR Immunostaining
nNegative (%)Weak (%)Moderate (%)Strong (%)p
Invasive breast carcinoma of no special typepT168813.129.934.922.10.0006
pT258717.932.933.415.8
pT3-411625.933.629.311.2
G116216.727.830.924.70.2624
G274416.830.434.118.7
G352114.434.234.516.9
pN064016.629.534.419.50.1622
pN+48515.935.731.816.7
pM018113.329.837.619.30.455
pM110619.831.133.016.0
HER2 negative79715.829.434.020.80.5939
HER2 positive11816.934.730.517.8
ER negative19313.034.738.913.50.0126
ER positive68217.228.932.321.7
PR negative36714.432.435.118.00.3353
PR positive54116.328.533.521.8
non-triple negative72217.529.232.321.10.0062
triple negative1279.436.240.913.4
Clear cell renal cell carcinomaISUP 12552.712.913.770.60.0066
ISUP 23744.511.516.867.1
ISUP 32451.613.524.560.4
ISUP 4680.017.625.057.4
Fuhrman 1603.35.015.076.70.0076
Fuhrman 26433.112.017.068.0
Fuhrman 32761.812.724.361.2
Fuhrman 4820.020.722.057.3
Thoenes 13322.112.016.069.90.0056
Thoenes 24623.714.120.361.9
Thoenes 3890.015.730.353.9
UICC 12982.39.414.473.8<0.0001
UICC 2350.014.328.657.1
UICC 3885.714.821.658.0
UICC 4684.422.133.839.7
pT16262.48.916.172.5<0.0001
pT21290.816.322.560.5
pT3-43113.917.723.854.7
pN01652.410.923.063.60.2419
pN+238.721.717.452.2
pM01044.89.616.369.20.0081
pM+863.519.830.246.5
Papillary renal cell carcinomaISUP 1340.017.632.450.00.8155
ISUP 21184.216.122.956.8
ISUP 3731.415.123.360.3
ISUP 470.014.328.657.1
Fuhrman 120.050.00.050.00.4008
Fuhrman 21614.314.923.657.1
Fuhrman 3750.013.324.062.7
Fuhrman 4110.09.136.454.5
Thoenes 1470.012.829.857.40.5469
Thoenes 21384.315.924.655.1
Thoenes 3166.312.518.862.5
UICC 1881.115.925.058.00.9823
UICC 2120.016.733.350.0
UICC 350.020.020.060.0
UICC 490.033.322.244.4
pT11852.711.924.960.50.0153
pT2444.518.229.547.7
pT3-4300.023.23.373.3
pN0230.013.017.469.60.8002
pN+120.016.725.058.3
pM0250.032.012.056.00.3955
pM+90.011.122.266.7
Urothelial bladder carcinomapTa G2 low3455.87.812.573.9<0.0001
pTa G2 high14821.69.513.555.4
pTa G38645.317.410.526.7
pT231222.411.25.860.60.1904
pT341419.111.610.958.5
pT420123.913.48.054.7
G27622.410.59.257.90.8354 *
G383521.212.18.458.3
pN044421.211.07.260.60.0051 *
pN+30925.216.510.447.9
L016225.910.56.856.80.0854 *
L117330.113.912.143.9
V027624.311.210.554.00.9963 *
V110024.012.010.054.0
UICC 1-21127.318.29.145.50.0466
UICC 3434.79.311.674.4
UICC 44025.017.515.042.5
Adenocarcinoma of the pancreaspT180.00.037.562.50.3759
pT2492.018.442.936.7
pT32950.013.246.840.0
pT4230.08.739.152.5
G1110.018.245.536.40.9853
G22660.413.245.940.6
G3800.012.548.838.8
pN0730.017.846.635.60.5177
pN+3010.312.345.541.9
Adenocarcinoma of the stomachdiffuse6552.335.49.23.10.1204
inestinal8246.329.320.73.7
mixed5133.331.429.45.9
pN06555.427.712.34.60.4248
pN+19944.732.718.64.0
MMR proficient22941.034.120.54.40.0051
MMR deficient3764.913.510.810.8
Endometrioid endometrial carcinomapT110579.016.23.81.00.2532
pT22365.234.80.00.0
pT3-43672.216.78.32.8
pN05066.030.04.00.00.0815
pN+3073.313.36.76.7
Serous carcinoma of the ovarypT1290.017.258.624.10.0720
pT2368.322.255.613.9
pT32314.823.839.831.6
pN0766.623.751.318.40.1145
pN11455.524.137.932.4
Germ cell tumors of the testispT133733.259.37.10.30.4978
pT213538.557.04.40.0
pT3-45240.457.71.90.0
V043332.360.76.70.20.0566
V15549.149.11.80.0
L037933.060.26.60.30.4164
L111540.055.74.30.0
spermatic cord invasion41034.159.56.10.20.7932
no spermatic cord invasion5637.558.93.60.0
rete testis invasion23430.862.07.30.00.1691
no rete testis invasion26237.857.34.60.4
pM052735.358.65.90.20.1508
pM+50.0100.00.00.0
Papillary carcinoma of the thyroidpT11360.03.740.455.90.453
pT2650.04.633.861.5
pT3-4900.06.745.647.8
pN0790.03.849.446.80.2827
pN+1040.07.739.452.9
Adenocarcinoma of the colorectumpT17981.016.52.50.00.3074
pT241582.214.52.41.0
pT3121383.314.72.00.1
pT442383.913.52.60.0
pN0111782.315.62.10.10.2084
pN+100883.713.42.50.4
V0153782.515.02.20.30.2568
V155684.213.12.70.0
L069282.515.22.00.30.8962
L1141483.013.12.40.2
right side44086.611.61.80.00.552
left side119084.513.52.00.0
MMR proficient111985.013.21.80.00.2494
MMR deficient8282.912.24.90.0
RAS wildtype45383.714.32.00.00.3056
RAS mutation35186.812.01.10.3
BRAF wildtype12183.514.91.70.00.5259
BRAF V600E mutation2290.99.10.00.0
* Only in pT2-4 urothelial bladder carcinomas. Abbreviations: pT: pathological tumor stage, G: grade, pN: pathological lymph node status, pM: pathological status of distant metastasis, V: venous invasion, L: lymphatic invasion, PR: progesterone receptor, MMR: mismatch repair, ER: estrogen receptor, ISUP: International Society of Urological Pathology, UICC: Union for International Cancer Control.
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Tsourlakis, M.C.; Kind, S.; Dwertmann Rico, S.; Weidemann, S.; Möller, K.; Schlichter, R.; Kluth, M.; Hube-Magg, C.; Bernreuther, C.; Sauter, G.; et al. Glucocorticoid Receptor (GR) Expression in Human Tumors: A Tissue Microarray Study on More than 14,000 Tumors. Biomedicines 2025, 13, 1683. https://doi.org/10.3390/biomedicines13071683

AMA Style

Tsourlakis MC, Kind S, Dwertmann Rico S, Weidemann S, Möller K, Schlichter R, Kluth M, Hube-Magg C, Bernreuther C, Sauter G, et al. Glucocorticoid Receptor (GR) Expression in Human Tumors: A Tissue Microarray Study on More than 14,000 Tumors. Biomedicines. 2025; 13(7):1683. https://doi.org/10.3390/biomedicines13071683

Chicago/Turabian Style

Tsourlakis, Maria Christina, Simon Kind, Sebastian Dwertmann Rico, Sören Weidemann, Katharina Möller, Ria Schlichter, Martina Kluth, Claudia Hube-Magg, Christian Bernreuther, Guido Sauter, and et al. 2025. "Glucocorticoid Receptor (GR) Expression in Human Tumors: A Tissue Microarray Study on More than 14,000 Tumors" Biomedicines 13, no. 7: 1683. https://doi.org/10.3390/biomedicines13071683

APA Style

Tsourlakis, M. C., Kind, S., Dwertmann Rico, S., Weidemann, S., Möller, K., Schlichter, R., Kluth, M., Hube-Magg, C., Bernreuther, C., Sauter, G., Marx, A. H., Simon, R., Bawahab, A. A., Lutz, F., Reiswich, V., Dum, D., Steurer, S., Burandt, E., Clauditz, T. S., ... Viehweger, F. (2025). Glucocorticoid Receptor (GR) Expression in Human Tumors: A Tissue Microarray Study on More than 14,000 Tumors. Biomedicines, 13(7), 1683. https://doi.org/10.3390/biomedicines13071683

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