Glucocorticoid Receptor Isoforms in Breast Cancer Raise Implications for Personalised Supportive Therapies
Abstract
1. Introduction
2. Results
2.1. GR Cellular Localisation and Staining Characteristics
2.2. Expression of GRtotal and GRβ Isoform in Breast Cancer Intrinsic Molecular and Main Histological Subtypes
2.3. Correlation of GR Staining with Clinicopathological Parameters in TNBC
3. Discussion
4. Materials and Methods
4.1. Samples, Pathological Characterisation, and Tissue Microarray Construction
4.2. Immunohistochemistry Staining and Scoring
4.3. Immunocytochemistry Following Transfection of Expression Vectors Encoding GR for Evaluation of Cellular Localisation
4.4. Statistical Methods
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Subtype Cohort | Prognostic Cohort | |||||
---|---|---|---|---|---|---|
Molecular Subtype | LumA | LumB-Her2- | LumB-Her2+ | Her2+ | TNBC | TNBC |
ER | pos | pos | pos | neg | neg | neg |
PR | pos | pos | pos/neg | neg | neg | neg |
Her2+ | neg | neg | pos | pos | neg | neg |
Ki-67 | <20% | ≥ 20% | nr | nr | nr | nr |
patient # | 36 | 53 | 46 | 12 | 47 | 161 |
patients’ age (years) | 60.9 | 58.5 | 58.8 | 55.6 | 57.4 | 55.7 |
(mean) | ||||||
(SD) | 11.1 | 13.3 | 14.1 | 15.3 | 14.8 | 12.7 |
(range) | 41–83 | 34–86 | 25–86 | 32–82 | 29–84 | 29–92 |
ER | PR | Her2 | GRt-cpl | GRt-nucl | GRβ-cpl | GRβ-nucl | |
---|---|---|---|---|---|---|---|
ER (n=196) | – | ||||||
PR (n = 196) | R = 0.72 p = 6.37 × 10−33 | – | |||||
Her2 (n = 196) | R = 0.02 p = 0.828 | R = −0.08 p = 0.274 | – | ||||
GRt-cpl (n = 193) | R = 0.24 p = 0.001 | R = 0.18 p = 0.012 | R = 0.12 p = 0.103 | – | |||
GRt-nucl (n = 196) | R = −0.13 p = 0.062 | R = −0.19 p = 0.007 | R = 0.01 p = 0.885 | R = 0.36 p = 2.48 × 10−7 | – | ||
GRβ-cpl (n = 184) | R = 0.13 p = 0.072 | R = 0.07 p = 0.339 | R = 0.21 p = 0.003 | R = 0.41 p = 1.52 × 10−8 | R = 0.18 p = 0.014 | – | |
GRβ-nucl (n = 186) | R = −0.10 p = 0.162 | R = −0.04 p = 0.555 | R = −0.11 p = 0.120 | R = 0.08 p = 0.261 | R = 0.20 p = 0.007 | R = 0.04 p = 0.554 | – |
Breast Cancer Subtype (Sample Number) | GR Staining | Ki67 Spearman R (95%CI); p Value | Number of Mitoses Per 10 Fields Spearman R (95%CI); p Value |
---|---|---|---|
LumA (n = 36) | GRt-cpl | −0.364 (−0.6280 to −0.02467); p = 0.032 | −0.258 (−0.5513 to 0.09299); p = 0.135 |
GRβ-cpl | −0.270 (−0.5773 to 0.1040); p = 0.142 | −0.223 (−0.5430 to 0.1531); p = 0.227 | |
TN (n = 161) | GRt-cpl | 0.206 (0.02810 to 0.3718); p = 0.020 | 0.111 (0.06454 to 0.3685); p = 0.004 |
GRβ-cpl | 0.320 (0.1479 to 0.4734); p = 0.001 | 0.204 (0.04445 to 0.3546); p = 0.010 |
Parameters | 10-Year PFS | p | 10-Year OS | p | ||
---|---|---|---|---|---|---|
(95% CI) | (95% CI) | |||||
age (years) | <62 | 74% (65–82) | 0.044 | 79% (71–87) | 0.025 | |
≥62 | 58% (45–71) | 63% (50–76) | ||||
type of surgery * | 1 | 77% (68–85) | 0.001 | 81% (73–88) | 0.002 | |
2 | 51% (38–65) | 58% (45–72) | ||||
vascular invasion | no | 79% (70–87) | <0.001 | 85% (77–93) | <0.001 | |
yes | 53% (41–66) | 57% (46–69) | ||||
perinodal invasion | no | 61% (44–78) | 0.034 | 65% (49–81) | 0.028 | |
yes | 36% (17–55) | 35% (16–54) | ||||
surgical margin (mm) | <1 | 46% (26–65) | 0.003 | <0.7 | 60% (41–79) | 0.061 |
≥1 | 72% (65–80) | ≥0.7 | 76% (68–83) | |||
Nottingham prognostic index | <3.58 | 82% (74–90) | <0.001 | <3.6 | 88% (81–95) | <0.001 |
≥3.58 | 49% (37–61) | ≥3.6 | 53% (41–65) | |||
tumour size (mm) | <29 | 75% (66–83) | <0.001 | <30 | 80% (73–87) | <0.001 |
≥29 | 49% (34–64) | ≥30 | 53% (37–68) | |||
pN | 0 | 78% (70–87) | <0.001 | 85% (78–93) | <0.001 | |
1 | 51% (38–64) | 53% (41–66) | ||||
positive/removed lymph node ratio | <0.087 | 77% (70–85) | <0.001 | <0.076 | 84% (77–91) | <0.001 |
≥0.087 | 42% (27–58) | ≥0.076 | 44% (30–59) | |||
stage | 1–2 | 75% (68–83) | <0.001 | 1–2a | 83% (75–90) | <0.001 |
3 | 28% (9–46) | 2b-3 | 52% (37–66) | |||
neutrophil count (109/l) | <2.89 | 36% (11–61) | 0.01 | <7.29 | 66% (56–75) | 0.064 |
≥2.89 | 67% (58–77) | ≥7.29 | 93% (79–100) | |||
SII (109/l) | <354 | 31% (4–59) | 0.019 | 65% (56–75) | 0.068 | |
≥354 | 67% (58–76) | 89% (74–100) | ||||
BMI | <29.8 | 63% (55–72) | 0.035 | 65% (53–77) | 0.086 | |
≥29.8 | 84% (70–97) | 78%/ (70–87) | ||||
adjuvant treatment | no or RT or ant | 45% (29–61) | <0.001 | 53% (38–69) | <0.001 | |
tax + ant ± RT | 68% (57–80) | 73% (62–84) | ||||
CMF ± RT or ant + RT | 83% (73–93) | 87% (78–96) | ||||
p53 | 0 | 40% (0–83) | 0.045 | 40% (0–83) | 0.021 | |
>0 | 90% (71–100) | 90% (71–100) | ||||
DCIS grade | 1–2 (or no DCIS) | 63% (51–75) | 0.08 | 65% (53–77) | 0.035 | |
3 (or necrosis) | 72% (62–81) | 79% (70–87) | ||||
body mass (kg) | <72 | 64% (54–73) | 0.117 | 67% (57–77) | 0.04 | |
≥72 | 75% (64–87) | 82% (73–91) | ||||
GRt-nuc | GRt-nucl-low (<65) | 81% (73–90) | 0.0185 | 85% (77–93) | 0.2433 | |
GRt-nucl-high (≥65) | 17% (−24–60) | 60% (29–92) | ||||
GRß-nuc | GRß-nucl-low (<30) | 81% (72–90) | 0.0659 | 87% (79–94) | 0.3747 | |
GRß-nucl-high (≥30) | 20% (−24–65) | 18% (2–34) | ||||
GRt-cpl | GRt-cpl-low (<2) | 82% (72–91) | 0.0949 | 87% (78–95) | 0.1547 | |
GRt-cpl-high (≥2) | 32% (11–52) | 48% (28–67) | ||||
GRß-cpl | GRß-cpl-low (<0.83) | 65% (54–76) | 0.5726 | 101% (86–116) | 0.2875 | |
GRß-cpl-high (≥0.83) | 81% (67–95) | 83% (74–92) | ||||
Ki-67 | <75 | 74% (65–83) | 0.06 | 67% (55–79) | 0.099 | |
≥75 | 37% (38–75) | 81% (72–91) | ||||
body height (cm) | <167 | 72% (64–81) | 0.062 | 77% (69–85) | 0.089 | |
≥167 | 56% (41–71) | 62% (48–77) |
Parameters | 10-Year OS HR (95% CI) | p | |
---|---|---|---|
Age (years) | <62 | 1 (ref.) | 0.116 |
≥62 | 1.81 (0.86–3.79) | ||
Positive/removed lymph node ratio | <0.076 | 1 (ref.) | p < 0.01 |
≥0.076 | 6.66 (2.93–15.1) | ||
SII (109/l) | <354 | 1 (ref.) | 0.345 |
≥354 | 0.58 (0.19–1.81) | ||
BMI | <29.8 | 1 (ref.) | 0.677 |
≥29.8 | 0.79 (0.26–2.42) | ||
DCIS grade | 1–2 (or DCIS < 10%) | 1 (ref.) | 0.017 |
3 (or necrosis) | 0.41 (0.19–0.85) | ||
Body weight (kg) | <72 | 1 (ref.) | 0.149 |
≥72 | 1.73 (0.82–3.63) | ||
GRß-cpl | low | 1 (ref.) | 0.036 |
high | 0.46 (0.22–0.95) |
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Butz, H.; Vereczki, V.; Budai, B.; Rubovszky, G.; Gyebrovszki, R.; Vida, R.; Szőcs, E.; Gerecs, B.; Kohánka, A.; Tóth, E.; et al. Glucocorticoid Receptor Isoforms in Breast Cancer Raise Implications for Personalised Supportive Therapies. Int. J. Mol. Sci. 2024, 25, 11813. https://doi.org/10.3390/ijms252111813
Butz H, Vereczki V, Budai B, Rubovszky G, Gyebrovszki R, Vida R, Szőcs E, Gerecs B, Kohánka A, Tóth E, et al. Glucocorticoid Receptor Isoforms in Breast Cancer Raise Implications for Personalised Supportive Therapies. International Journal of Molecular Sciences. 2024; 25(21):11813. https://doi.org/10.3390/ijms252111813
Chicago/Turabian StyleButz, Henriett, Viktória Vereczki, Barna Budai, Gábor Rubovszky, Rebeka Gyebrovszki, Ramóna Vida, Erika Szőcs, Bence Gerecs, Andrea Kohánka, Erika Tóth, and et al. 2024. "Glucocorticoid Receptor Isoforms in Breast Cancer Raise Implications for Personalised Supportive Therapies" International Journal of Molecular Sciences 25, no. 21: 11813. https://doi.org/10.3390/ijms252111813
APA StyleButz, H., Vereczki, V., Budai, B., Rubovszky, G., Gyebrovszki, R., Vida, R., Szőcs, E., Gerecs, B., Kohánka, A., Tóth, E., Likó, I., Kacskovics, I., & Patócs, A. (2024). Glucocorticoid Receptor Isoforms in Breast Cancer Raise Implications for Personalised Supportive Therapies. International Journal of Molecular Sciences, 25(21), 11813. https://doi.org/10.3390/ijms252111813