AR/ER Ratio Correlates with Expression of Proliferation Markers and with Distinct Subset of Breast Tumors
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Population
2.2. Immunohistochemistry (IHC)
2.3. RNA Extraction
2.4. Reverse-Transcription PCR (RT-PCR)
2.5. qPCR Assays
2.6. Validation Cohort
2.7. AR-Ness Signature on Validation Cohort
2.8. Statistical Analyses
3. Results
3.1. Patients and Tumor Characteristics
3.2. Assessment of AR/ER Ratio
3.3. Association of AR/ER Ratio with Genes Involved in BC Proliferation
3.4. Association of AR/ER Ratio with Cellular Proliferation in Validation Cohort
3.5. AR-Ness Signature Evaluation in Validation Cohort
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristics | ER + n (%) | ER − n (%) | P Value (Fisher Test) | |
---|---|---|---|---|
Total number of patients | 47 | 9 | - | |
Median age (Interval) | 62 (35–82) | 60 (43–78) | 0.591 * | |
Tumor Size (missing 1 case) | <20 mm | 17 (36.2) | - | 0.028 |
≥20 mm | 30 (63.8) | 9 (100) | ||
Metastatic Lymph nodes | pN0 | 22 (46.8) | 7 (77.8) | 0.230 |
pN1–3 | 14 (29.8) | 1 (11.1) | ||
pN > 3 | 11 (23.4) | 1 (11.1) | ||
Grading | 1 | 4 (8.5) | - | 0.085 |
2 | 20 (42.6) | 1 (11.1) | ||
3 | 23 (48.9) | 8 (88.9) | ||
Histotype | IDC-NST | 36 (76.6) | 5 (55.6) | 0.245 |
ILC | 2 (4.3) | - | ||
Mixed type | 5 (10.6) | - | ||
others | 4 (8.5) | 4 (44.4) | ||
Vascular invasion | No | 7 (14.9) | 3 (33.3) | 0.192 |
Yes | 40 (85.1) | 6 (66.7) | ||
PgR | 0 | 17 (36.2) | 9 (100) | <0.0001 |
≥1 | 30 (63.8) | - | ||
Ki67 | <20% | 14 (29.8) | 1 (11.1) | 0.235 |
≥20% | 33 (70.2) | 8 (88.9) | ||
HER2 | Negative | 36 (76.6) | 6 (66.7) | 0.399 |
Positive | 11 (23.4) | 3 (33.3) | ||
AR | 0 | 6 (12.8) | 3 (33.3) | 0.148 |
≥1% | 41 (87.2) | 6 (66.7) | ||
IHC – Surrogate Subtype | Luminal A-Like | 12 (25.5) | - | <0.0001 |
Luminal B-Like (HER2-) | 24 (51.1) | - | ||
Luminal B-Like (HER2+) | 11 (23.4) | - | ||
HER2+/ER- | - | 3 (33.3) | ||
TNBC | - | 6 (66.7) |
Characteristics | AR/ER < 2 n (%) | AR/ER > 2 n (%) | P Value (Fisher Test) | |
---|---|---|---|---|
Total number of patients | 37 (78.7) | 10(21.3) | - | |
Median Age (Interval) | 62 (35–79) | 65 (47–82) | 0.309 * | |
Grading | 1 | 3 (8.1) | 1 (10) | 0.215 |
2 | 18 (48.6) | 2 (20) | ||
3 | 43 (16.1) | 7 (70) | ||
Tumor size | <20 mm | 12 (33.3) | 4 (40) | 0.485 |
≥20 mm | 24 (66.7) | 6 (60) | ||
Metastatic Lymph nodes | 0 | 20 (54.1) | 2 (20) | 0.108 |
1–3 | 9 (24.3) | 5 (50) | ||
>3 | 8 (21.6) | 3 (30) | ||
Vascular invasion | No | 4 (10.8) | 3 (30) | 0.155 |
Yes | 33 (89.2) | 7 (70) | ||
PgR | <20% | 26 (70.3) | 4 (40) | 0.136 |
≥20% | 11 (29.7) | 6 (60) | ||
Ki-67 | <20% | 12 (32.4) | 2 (20) | 0.366 |
≥20% | 25 (67.6) | 8 (80) | ||
HER2 Status | Negative | 32 (86.5) | 4 (40) | 0.01 |
Positive | 5 (13.5) | 6 (60) | ||
ER% | Mean (interval) | 78 (2–99) | 21 (2–50) | <0.001 * |
AR% | Mean (interval) | 70 (0–99) | 83 (50–100) | 0.319 * |
IHC – Surrogate Subtype | Luminal A | 12 (32.4) | 0 (0) | 0.004 |
Luminal B-Like (HER2-) | 20 (54.1) | 4 (40) | ||
Luminal B-Like (HER2+) | 5 (13.5) | 6 (60) |
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Rangel, N.; Rondon-Lagos, M.; Annaratone, L.; Aristizábal-Pachon, A.F.; Cassoni, P.; Sapino, A.; Castellano, I. AR/ER Ratio Correlates with Expression of Proliferation Markers and with Distinct Subset of Breast Tumors. Cells 2020, 9, 1064. https://doi.org/10.3390/cells9041064
Rangel N, Rondon-Lagos M, Annaratone L, Aristizábal-Pachon AF, Cassoni P, Sapino A, Castellano I. AR/ER Ratio Correlates with Expression of Proliferation Markers and with Distinct Subset of Breast Tumors. Cells. 2020; 9(4):1064. https://doi.org/10.3390/cells9041064
Chicago/Turabian StyleRangel, Nelson, Milena Rondon-Lagos, Laura Annaratone, Andrés Felipe Aristizábal-Pachon, Paola Cassoni, Anna Sapino, and Isabella Castellano. 2020. "AR/ER Ratio Correlates with Expression of Proliferation Markers and with Distinct Subset of Breast Tumors" Cells 9, no. 4: 1064. https://doi.org/10.3390/cells9041064
APA StyleRangel, N., Rondon-Lagos, M., Annaratone, L., Aristizábal-Pachon, A. F., Cassoni, P., Sapino, A., & Castellano, I. (2020). AR/ER Ratio Correlates with Expression of Proliferation Markers and with Distinct Subset of Breast Tumors. Cells, 9(4), 1064. https://doi.org/10.3390/cells9041064