Hormonal Receptor Status Determines Prognostic Significance of FGFR2 in Invasive Breast Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Low FGFR2 Expression Is Associated with Unfavorable Clinicopathological Characteristics Including Negative Hormonal Receptor Status
2.2. Low FGFR2 Protein Is Associated with Poor Overall and Disease-Free Survival
2.3. Subclassification of ER+ Patients by PR(mol) Supports Association of PR-Negativity with Unfavorable Clinicopathological Characteristics
2.4. PR(mol) Status Does Not Affect Prognostic Value of FGFR2
2.5. Low FGFR2 Gene mRNA Level Is Associated with Poor Overall and Relapse-Free Survival—In Silico Confirmation
3. Discussion
4. Materials and Methods
4.1. Patient Selection and Collection of Histopathological and Clinical Data
4.2. Immunohistochemistry for FGFR2
4.3. RNA Quantification
4.4. In Silico Analysis of TCGA Data
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variable | Whole Group n = 353 (100) | ER−PR− n = 34 (9.6) | ER+PR− n = 73 (20.7) | ER+PR+ n = 246 (69.7) | p-Value |
---|---|---|---|---|---|
Age (years) 1 | 63.8 | 63.6 | 64.7 | 63.6 | 0.132 |
(55.0–71.3) | (55.7–73.1) | (60.0–70.6) | (52.7–70.8) | ||
Menopausal status 2 | 0.063 | ||||
Pre | 37 (11.4) | 2 (6.1) | 3 (4.6) | 32 (14.1) | |
Post | 288 (88.6) | 31 (93.9) | 62 (95.4) | 195 (85.9) | |
Grade 2 | <0.001 * | ||||
1 | 42 (11.9) | 2 (5.9) | 9 (12.3) | 31 (12.6) | |
2 | 227 (64.3) | 12 (35.3) | 43 (58.9) | 168 (69.9) | |
3 | 84 (23.8) | 20 (58.8) | 21 (28.8) | 42 (17.5) | |
Ki67 (%) 1 | 18.0 | 32.0 | 20.0 | 12.0 | 0.011 * |
(5.0–30.0) | (30.5–35.5) | (10.0–40.0) | (5.0–25.0) | ||
HER2 amplification positivity 2 | 45 (12.7) | 12 (35.3) | 13 (17.8) | 20.0 (8.1) | <0.001 * |
Tumor size (mm) 1 | 20.0 | 25.0 | 25.0 | 20.0 | 0.004 * |
(15.0–27.0) | (15.0–35.0) | (19.0–30.0) | (15.0–25.0) | ||
T feature 2 | 0.064 | ||||
pT1 | 143 (53.0) | 13 (40.6) | 15 (38.5) | 115 (57.8) | |
pT2 | 116 (43.0) | 16 (50.0) | 22 (56.4) | 78 (39.2) | |
pT3-4 | 11 (4.0) | 3 (9.4) | 2 (5.1) | 6 (3.0) | |
Metastases present 2 | 116 (33.5) | 13 (42.4) | 25 (34.7) | 77 (32.0) | 0.475 |
N feature 2 | 0.733 | ||||
pN0 | 230 (66.5) | 17 (57.6) | 47 (65.3) | 164 (68.0) | |
pN1 | 81 (23.4) | 10 (30.3) | 16 (22.2) | 55 (22.8) | |
pN2-3 | 34 (10.1) | 4 (12.1) | 9 (12.5) | 22 (9.1) | |
Staging 2 | 0.289 | ||||
Very early (IA) | 135 (39.1) | 11 (34.4) | 23 (31.9) | 101 (41.9) | |
Early (IB-IIIA) | 189 (54.8) | 17 (53.1) | 45 (62.5) | 127 (52.7) | |
Advanced (IIIB-IV) | 21 (6.1) | 4 (12.5) | 4 (5.6) | 13 (5.4) | |
Multifocality 2 | 39 (14.3) | 3 (8.8) | 6 (15.4) | 30 (15.0) | 0.622 |
DCIS present 2 | 103 (29.1) | 10 (29.4) | 23 (31.5) | 70 (28.3) | 0.871 |
Hormonotherapy 2 | 220 (81.2) | 0 (0.0) | 46 (82.1) | 174 (86.6) | <0.001 * |
Neoadjuvant therapy 2 | 231 (75.5) | 26 (89.7) | 30 (48.4) | 175 (81.4) | <0.001 * |
Adjuvant chemotherapy 2 | 150 (62.2) | 25 (80.7) | 38 (66.7) | 87 (56.9) | 0.032 * |
Adjuvant radiotherapy 2 | 151 (64.8) | 11 (50.0) | 30 (61.2) | 110 (67.9) | 0.111 |
Progression/relapse 3 | 30 (9.8) | 10 (31.3) | 8 (11.9) | 12 (5.8) | <0.001 * |
Disease-free survival (years) | 3.9 (2.7–6.4) | 3.6 (2.2–4.5) | 3.8 (2.5–4.9) | 4.2 (2.9–6.6) | |
Deaths 3 | 41 (11.6) | 10 (29.4) | 6 (8.2) | 25 (10.1) | <0.001 * |
Overall survival (years) | 4.2 (2.9–6.5) | 3.6 (2.6–4.5) | 4.0 (2.7–5.5) | 4.7 (3.0–6.7) |
Variable | FGFR2low n = 117 (33.1) | FGFR2high n = 236 (66.9) | p-Value |
---|---|---|---|
Age (years) 1 | 64.6 (56.5–75.2) | 63.4 (54.2–69.9) | 0.078 |
Menopausal status 2 | 0.078 | ||
Pre | 8 (7.1) | 29 (13.7) | |
Post | 104 (92.9) | 183 (86.3) | |
Grade 2 | <0.001 * | ||
1 | 7 (5.9) | 35 (14.8) | |
2 | 65 (55.6) | 162 (68.6) | |
3 | 45 (38.5) | 39 (16.5) | |
Ki67 (%) 1 | 23.5 (12.0–40.0) | 15.0 (5.0–28.0) | 0.014 * |
HER2 amplification positivity 2 | 11 (9.4) | 33 (14.0) | 0.220 |
Hormonal status 2 | <0.001 * | ||
ER−PR− | 25 (21.4) | 9 (3.8) | |
ER+PR− | 22 (18.8) | 51 (21.6) | |
ER+PR+ | 70 (59.8) | 176 (74.6) | |
PR molecular status 2 | 0.757 | ||
PR(mol+) | 59 (66.3) | 145 (64.4) | |
PR(mol-) | 30 (33.7) | 80 (35.6) | |
Tumor size (mm) 1 | 20.0 (15.0–30.0) | 20.0 (15.0–25.0) | 0.898 |
T feature 2 | 0.731 | ||
pT1 | 55 (51.4) | 88 (54.0) | |
pT2 | 46 (43.0 | 69 (42.3) | |
pT3-4 | 6 (5.6) | 6 (3.7) | |
Metastases present 2 | 44 (38.6) | 76 (32.9) | 0.296 |
N feature 2 | 0.682 | ||
pN0 | 73 (64.0) | 156 (67.5) | |
pN1 | 30 (26.3) | 51 (22.1) | |
pN2-3 | 11 (9.6) | 24 (10.4) | |
Staging 2 | 0.234 | ||
Very early (IA) | 40 (35.1) | 95 (41.1) | |
Early (IB-IIIA) | 69 (60.5) | 119 (51.5) | |
Advanced (IIIB-IV) | 5 (4.4) | 17 (7.4) | |
DCIS present 2 | 30 (25.6) | 72 (30.5) | 0.342 |
DFS events 3 | 25 (24.8) | 22 (10.8) | 0.005 * |
Disease-free survival (years) | 3.9 (2.6–6.6) | 3.9 (2.7–5.8) | |
Deaths 3 | 23 (19.7) | 18 (7.6) | 0.003 * |
Overall survival (years) | 4.6 (2.7–6.7) | 4.1 (2.9–6.4) |
Outcome | HR (95% CI) Raw | HR (95% CI) Adjusted for Hormonal Status | HR (95% CI) Adjusted for Hormonal Status, Age and Tumor Size |
---|---|---|---|
OS (FGFR2high as reference) | 2.34 (1.26–4.34), p = 0.007 | 2.09 (1.08–4.04), p = 0.028 | 1.45 (0.73–2.90), p = 0.283 |
DFS (FGFR2high as reference) | 2.22 (1.25–3.93), p = 0.006 | 1.92 (1.03–3.56), p = 0.038 | 1.25 (0.66–2.37), p = 0.496 |
Hormonal Status | PR(mol+) | PR(mol−) |
---|---|---|
ER−PR− | 0 (0.0%) | 32 (100.0%) |
ER+PR− | 10 (13.7%) | 63 (86.3%) |
ER+PR+ | 194 (80.6%) | 47 (19.4%) |
All | 204 (59.1%) | 142 (40.9%) |
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Braun, M.; Piasecka, D.; Tomasik, B.; Mieczkowski, K.; Stawiski, K.; Zielinska, A.; Kopczynski, J.; Nejc, D.; Kordek, R.; Sadej, R.; et al. Hormonal Receptor Status Determines Prognostic Significance of FGFR2 in Invasive Breast Carcinoma. Cancers 2020, 12, 2713. https://doi.org/10.3390/cancers12092713
Braun M, Piasecka D, Tomasik B, Mieczkowski K, Stawiski K, Zielinska A, Kopczynski J, Nejc D, Kordek R, Sadej R, et al. Hormonal Receptor Status Determines Prognostic Significance of FGFR2 in Invasive Breast Carcinoma. Cancers. 2020; 12(9):2713. https://doi.org/10.3390/cancers12092713
Chicago/Turabian StyleBraun, Marcin, Dominika Piasecka, Bartlomiej Tomasik, Kamil Mieczkowski, Konrad Stawiski, Aleksandra Zielinska, Janusz Kopczynski, Dariusz Nejc, Radzislaw Kordek, Rafal Sadej, and et al. 2020. "Hormonal Receptor Status Determines Prognostic Significance of FGFR2 in Invasive Breast Carcinoma" Cancers 12, no. 9: 2713. https://doi.org/10.3390/cancers12092713