Role of IL-17A and IL-17RA in Prostate Cancer with Lymph Nodes Metastasis: Expression Patterns and Clinical Significance
Abstract
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients Selection
2.2. Tissue Microarrays (TMAs) and Immunohistochemical (IHC) Staining
2.3. Statistical Analysis
3. Results
3.1. IL-17A
3.2. IL-17RA
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
BMI | body mass index |
EAU | European Association of Urology |
ECE | extracapsular extension |
EMT | epithelial-to-mesenchymal transition |
GGG ISUP | International Society of Urological Pathology grade (group) system |
HE | hematoxylin and eosin |
IHC | immunohistochemistry |
IL | interleukin |
IRS | immunoreactive scale |
LN+ | metastatic/positive lymph node |
LVI | lymphovascular invasion |
MMP7 | matrix metalloproteinase 7 |
MSKCC | Memorial Sloan Kettering Cancer Center |
NVI | neurovascular invasion |
PCa | prostate cancer |
PIN | prostatic intraepithelial neoplasia |
PSA | prostate-specific antigen |
pT | pathological tumor stage |
RP | radical prostatectomy |
TMA | tissue microarray |
TURP | transurethral resection of the prostate |
References
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Immunoreactive Scale (IRS) | |||
A—Percentage of Positive Cancer Cells | B—Staining Intensity | ||
Score | Score | ||
0 | no cells with positive reaction | 0 | no color reaction |
1 | <10% cells with positive reaction | 1 | mild reaction |
2 | 10–50% cells with positive reaction | 2 | moderate reaction |
3 | 51–80% cells with positive reaction | 3 | intense reaction |
4 | >80% cells with positive reaction | ||
IRS SCORE (A X B): 0–12 points | |||
Final score | Level of expression | ||
1–7 | Low expression | ||
8–12 | High expression |
Variable | Statistics |
---|---|
General characteristics of patients | |
Age (years): | |
M ± SD | 64.9 ± 5.5 |
BMI (kg/m2): | |
M ± SD | 28.1 ± 3.7 |
Preoperative PSA (ng/mL): | |
Me (Q1; Q3) | 19.8 (12; 36.1) |
EAU risk group, n (%): | |
Low-risk | 1 (1.3) |
Intermediate-risk | 8 (10.4) |
High-risk | 38 (49.3) |
High-risk locally advanced | 30 (39) |
Clinicopathological parameters | |
pT, n (%): | |
2a | 1 (1.3) |
2c | 9 (11.7) |
3a | 14 (18.2) |
3b | 53 (68.8) |
Postoperative Gleason, n (%): | |
3 + 3 | 1 (1.3) |
3 + 4 | 10 (13) |
3 + 5 | 4 (5.2) |
4 + 3 | 19 (24.7) |
4 + 4 | 3 (3.9) |
4 + 5 | 29 (37.6) |
5 + 3 | 2 (2.6) |
5 + 4 | 8 (10.4) |
5 + 5 | 1 (1.3) |
Postoperative GGG ISUP, n (%): | |
1 | 1 (1.3) |
2 | 10 (13) |
3 | 19 (24.7) |
4 | 9 (11.7) |
5 | 38 (48.3) |
Extracapsular extension of prostate, n (%): | |
Yes | 66 (85.7) |
No | 11 (14.3) |
Extracapsular extension of lymph node, n (%): | |
Yes | 19 (24.7) |
No | 58 (75.3) |
Resection margin, n (%): | |
Positive | 54 (70.1) |
Negative | 23 (29.9) |
Neurovascular invasion, n (%): | |
Yes | 70 (90.9) |
No | 1 (1.3) |
No data | 6 (7.8) |
Lymphovascular invasion, n (%): | |
Yes | 57 (74) |
No | 15 (19.5) |
No data | 5 (6.5) |
Affected lymph nodes (%): | |
Me (Q1; Q3) | 12.5 (8.3; 27.3) |
Radical procedure, n (%): | |
Yes | 36 (46.7) |
No | 41 (53.3) |
Expression (IRS Scale) | ||||||
---|---|---|---|---|---|---|
IL-17A | IL-17RA | |||||
Prostate | Metastatic Lymph Node | p-Value | Prostate | Metastatic Lymph Node | p-Value | |
A—Percentage of positively stained cancer cells (score) | 0.634 | 0.271 | ||||
Me (Q1; Q3) | 4 [3; 4] | 4 [3; 4] | 3 [3; 4] | 3 [2; 4] | ||
Min–Max | 0–4 | 2–4 | 0–4 | 0–4 | ||
B—Intensity of staining (score) | 0.446 | 0.112 | ||||
Me (Q1; Q3) | 2 [2; 3] | 2 [2; 3] | 1 [1; 2] | 1 [1; 1] | ||
Min–Max | 0–3 | 1–3 | 0–3 | 0–3 | ||
IRS score (A × B) | 0.415 | 0.009 | ||||
Me (Q1; Q3) | 8 [6; 12] | 8 [6; 9] | 4 [3; 6] | 3 [2; 4] | ||
Min–Max | 0–12 | 2–12 | 0–12 | 0–12 | ||
Expression level: | 0.308 | 0.012 | ||||
Low expression (1–7 score), n (%) | 19 (25) | 25 (32.5) | 52 (74.3) | 65 (90.3) | ||
High expression (8–12 score), n (%) | 57 (75) | 52 (67.5) | 18 (25.7) | 7 (9.7) |
IL-17A | IL-17RA | |||||||
---|---|---|---|---|---|---|---|---|
Prostate | Metastatic Lymph Node | Prostate | Metastatic Lymph Node | |||||
rho | p | rho | p | rho | p | rho | p | |
Preoperative PSA (ng/mL) | 0.033 | 0.778 | 0.027 | 0.813 | 0.057 | 0.623 | 0.100 | 0.387 |
Affected lymph nodes (%) | −0.007 | 0.952 | 0.312 | 0.006 | 0.100 | 0.385 | 0.144 | 0.211 |
Age (years) | −0.037 | 0.752 | −0.037 | 0.749 | 0.047 | 0.682 | 0.019 | 0.873 |
BMI (kg/m2) | 0.251 | 0.028 | 0.013 | 0.912 | 0.096 | 0.404 | 0.079 | 0.494 |
EAU risk group | 0.159 | 0.168 | 0.376 | 0.001 | 0.051 | 0.660 | 0.229 | 0.045 |
Postoperative GGG ISUP | −0.020 | 0.862 | 0.146 | 0.205 | −0.111 | 0.335 | −0.023 | 0.841 |
IL-17A Expression Level (IRS Score-Based) | |||||||
---|---|---|---|---|---|---|---|
Variables | Expression of IL-17A in PROSTATE | Expression of IL-17A in METASTATIC LYMPH NODE | |||||
Level of Expression | p-Value | Level of Expression | p-Value | ||||
Low (N = 19) | High (N = 57) | Low (N = 25) | High (N = 52) | ||||
n (%) | n (%) | n (%) | n (%) | ||||
pT | 3a and 3b | 15 (79.0%) | 51 (89.5%) | 0.257 | 20 (80.0%) | 47 (90.4%) | 0.279 |
2a and 2c | 4 (21.0%) | 6 (10.5%) | 5 (20.0%) | 5 (9.6%) | |||
ECE of prostate | Yes | 16 (84.2%) | 49 (86.0%) | 1.000 | 18 (72.0%) | 48 (92.3%) | 0.033 |
No | 3 (15.8%) | 8 (14.0%) | 7 (28.0%) | 4 (7.7%) | |||
Resection margin | Positive | 11 (57.9%) | 42 (73.7%) | 0.251 | 18 (72.0%) | 36 (69.2%) | 0.986 |
Negative | 8 (42.1%) | 15 (26.3%) | 7 (28.0%) | 16 (30.8%) | |||
ECE of lymph node | Yes | 6 (31.6%) | 13 (22.8%) | 0.543 | 3 (12.0%) | 16 (30.8%) | 0.094 |
No | 13 (68.4%) | 44 (77.2%) | 22 (88.0%) | 36 (69.2%) | |||
NVI | Yes | 16 (100.0%) | 53 (98.2%) | 1.000 | 20 (95.2%) | 50 (100.0%) | 0.296 |
No | 0 (0.0%) | 1 (1.8%) | 1 (4.8%) | 0 (0.0%) | |||
LVI | Yes | 12 (80.0%) | 44 (78.6%) | 1.000 | 16 (69.6%) | 41 (83.7%) | 0.288 |
No | 3 (20.0%) | 12 (21.4%) | 7 (30.4%) | 8 (16.3%) | |||
Radical procedure | Yes | 7 (43.8%) | 28 (58.3%) | 0.389 | 12 (57.1%) | 24 (54.5%) | 0.944 |
No | 9 (56.3%) | 20 (41.7%) | 9 (42.9%) | 20 (45.5%) | |||
Expression of IL-17A in metastatic lymph node | Low | 8 (42.1%) | 16 (28.1%) | 0.287 | XX | XX | XX |
High | 11 (57.9%) | 41 (71.9%) | XX | XX | |||
Expression of IL-17A in prostate | Low | XX | XX | XX | 8 (33.3%) | 11 (21.2%) | 0.178 |
High | XX | XX | 16 (66.7%) | 41 (78.8%) |
IL-17RA Expression Level (IRS Score-Based) | |||||||
---|---|---|---|---|---|---|---|
Variables | Expression of IL-17RA in PROSTATE | Expression of IL-17RA in METASTATIC LYMPH NODE | |||||
Level of Expression | p-Value | Level of Expression | p-Value | ||||
Low (N = 52) | High (N = 18) | Low (N = 65) | High (N = 7) | ||||
n (%) | n (%) | n (%) | n (%) | ||||
pT | 3a and 3b | 45 (86.5%) | 16 (88.9%) | 1.000 | 57 (87.7%) | 6 (85.7%) | 1.000 |
2a and 2c | 7 (13.5%) | 2 (11.1%) | 8 (12.3%) | 1 (14.3%) | |||
ECE of prostate | Yes | 47 (90.4%) | 14 (77.8%) | 0.222 | 58 (89.2%) | 5 (71.4%) | 0.209 |
No | 5 (9.6%) | 4 (22.2%) | 7 (10.8%) | 2 (28.6%) | |||
Resection margin | Positive | 37 (71.2%) | 13 (72.2%) | 1.000 | 45 (69.2%) | 6 (85.7%) | 0.665 |
Negative | 15 (28.8%) | 5 (27.8%) | 20 (30.8%) | 1 (14.3%) | |||
ECE of lymph node | Yes | 13 (25.0%) | 3 (16.7%) | 0.745 | 13 (20.0%) | 5 (71.4%) | 0.009 |
No | 39 (75.0%) | 15 (83.3%) | 52 (80.0%) | 2 (28.6%) | |||
NVI | Yes | 45 (97.8%) | 18 (100.0%) | 1.000 | 59 (100.0%) | 7 (100.0%) | 1.000 |
No | 1 (2.2%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | |||
LVI | Yes | 40 (81.6%) | 12 (70.6%) | 0.491 | 48 (80.0%) | 6 (85.7%) | 1.000 |
No | 9 (18.4%) | 5 (29.4%) | 12 (20.0%) | 1 (14.3%) | |||
Radical procedure | Yes | 25 (58.1%) | 8 (50.0%) | 0.769 | 31 (57.4%) | 2 (33.3%) | 0.394 |
No | 18 (41.9%) | 8 (50.0%) | 23 (42.6%) | 4 (66.7%) | |||
Expression of IL-17RA in metastatic lymph node | Low | 43 (87.8%) | 16 (94.1%) | 0.667 | XX | XX | XX |
High | 6 (12.2%) | 1 (5.9%) | XX | XX | |||
Expression of IL-17RA in prostate | Low | XX | XX | XX | 43 (72.9%) | 6 (85.7%) | 0.667 |
High | XX | XX | 16 (27.1%) | 1 (14.3%) |
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Kiełb, P.; Kaczorowski, M.; Kowalczyk, K.; Piotrowska, A.; Nowak, Ł.; Krajewski, W.; Chorbińska, J.; Dudek, K.; Dzięgiel, P.; Hałoń, A.; et al. Role of IL-17A and IL-17RA in Prostate Cancer with Lymph Nodes Metastasis: Expression Patterns and Clinical Significance. Cancers 2023, 15, 4578. https://doi.org/10.3390/cancers15184578
Kiełb P, Kaczorowski M, Kowalczyk K, Piotrowska A, Nowak Ł, Krajewski W, Chorbińska J, Dudek K, Dzięgiel P, Hałoń A, et al. Role of IL-17A and IL-17RA in Prostate Cancer with Lymph Nodes Metastasis: Expression Patterns and Clinical Significance. Cancers. 2023; 15(18):4578. https://doi.org/10.3390/cancers15184578
Chicago/Turabian StyleKiełb, Paweł, Maciej Kaczorowski, Kamil Kowalczyk, Aleksandra Piotrowska, Łukasz Nowak, Wojciech Krajewski, Joanna Chorbińska, Krzysztof Dudek, Piotr Dzięgiel, Agnieszka Hałoń, and et al. 2023. "Role of IL-17A and IL-17RA in Prostate Cancer with Lymph Nodes Metastasis: Expression Patterns and Clinical Significance" Cancers 15, no. 18: 4578. https://doi.org/10.3390/cancers15184578
APA StyleKiełb, P., Kaczorowski, M., Kowalczyk, K., Piotrowska, A., Nowak, Ł., Krajewski, W., Chorbińska, J., Dudek, K., Dzięgiel, P., Hałoń, A., Szydełko, T., & Małkiewicz, B. (2023). Role of IL-17A and IL-17RA in Prostate Cancer with Lymph Nodes Metastasis: Expression Patterns and Clinical Significance. Cancers, 15(18), 4578. https://doi.org/10.3390/cancers15184578