Inflammation and Prostate Cancer: Pathological Analysis from Pros-IT CNR 2
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Patient’s Features
2.3. Pathological Features
2.4. Statistical Analysis
3. Results
3.1. Baseline Characteristics of Patients
3.2. Characteristics of Cores among Patients with PCa
3.3. The Relationship between Inflammation and Neoplasm for Each Core
3.4. Follow up and Risk of BCR
4. Discussion
5. Conclusions
6. Pros-IT2 Study Group
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- EAU. EAU Guidelines, Proceedings of the EAU Annual Congress Amsterdam 2022, Amsterdam, The Netherlands, 1–4 July 2022; EAU: Arnhem, The Netherlands, 2022; ISBN 978-94-92671-16-5. [Google Scholar]
- Taverna, G.; Pedretti, E.; Di Caro, G.; Borroni, E.M.; Marchesi, F.; Grizzi, F. Inflammation and prostate cancer: Friends or foe? Inflamm. Res. 2015, 64, 275–286. [Google Scholar] [CrossRef] [PubMed]
- Gandaglia, G.; Briganti, A.; Gontero, P.; Mondaini, N.; Novara, G.; Salonia, A.; Sciarra, A.; Montorsi, F. The role of chronic prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH). BJU Int. 2013, 112, 432–441. [Google Scholar] [CrossRef] [PubMed]
- De Nunzio, C.; Salonia, A.; Gacci, M.; Ficarra, V. Inflammation is a target of medical treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia. World J. Urol. 2020, 38, 2771–2779, Erratum in World J. Urol. 2020, 38, 2781. [Google Scholar] [CrossRef] [PubMed]
- Samarinas, M.; Gacci, M.; de la Taille, A.; Gravas, S. Prostatic inflammation: A potential treatment target for male LUTS due to benign prostatic obstruction. Prostate Cancer Prostatic Dis. 2018, 21, 161–167. [Google Scholar] [CrossRef] [PubMed]
- Vignozzi, L.; Rastrelli, G.; Corona, G.; Gacci, M.; Forti, G.; Maggi, M. Benign prostatic hyperplasia: A new metabolic disease? J. Endocrinol. Investig. 2014, 37, 313–322. [Google Scholar] [CrossRef] [PubMed]
- Vral, A.; Magri, V.; Montanari, E.; Gazzano, G.; Gourvas, V.; Marras, E.; Perletti, G. Topographic and quantitative relationship between prostate inflammation, proliferative inflammatory atrophy and low-grade prostate intraepithelial neoplasia: A biopsy study in chronic prostatitis patients. Int. J. Oncol. 2012, 41, 1950–1958. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Platz, E.A.; De Marzo, A.M. Epidemiology of inflammation and prostate cancer. J. Urol. 2004, 171 Pt 2, S36–S40. [Google Scholar] [CrossRef] [PubMed]
- Rani, A.; Dasgupta, P.; Murphy, J.J. Prostate Cancer: The Role of Inflammation and Chemokines. Am. J. Pathol. 2019, 189, 2119–2137. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cai, T.; Santi, R.; Tamanini, I.; Galli, I.C.; Perletti, G.; Bjerklund Johansen, T.E.; Nesi, G. Current Knowledge of the Potential Links between Inflammation and Prostate Cancer. Int. J. Mol. Sci. 2019, 20, 3833. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bilusic, M.; Madan, R.A.; Gulley, J.L. Immunotherapy of Prostate Cancer: Facts and Hopes. Clin. Cancer Res. 2017, 23, 6764–6770. [Google Scholar] [CrossRef] [PubMed]
- de Bono, J.S.; Guo, C.; Gurel, B.; De Marzo, A.M.; Sfanos, K.S.; Mani, R.S.; Gil, J.; Drake, C.G.; Alimonti, A. Prostate carcinogenesis: Inflammatory storms. Nat. Rev. Cancer 2020, 20, 455–469. [Google Scholar] [CrossRef] [PubMed]
- Bishop, J.L.; Thaper, D.; Zoubeidi, A. The Multifaceted Roles of STAT3 Signaling in the Progression of Prostate Cancer. Cancers 2014, 6, 829–859. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Noale, M.; Maggi, S.; Artibani, W.; Bassi, P.F.; Bertoni, F.; Bracarda, S.; Conti, G.N.; Corvò, R.; Gacci, M.; Graziotti, P.; et al. Pros-IT CNR: An Italian prostate cancer monitoring project. Aging Clin. Exp. Res. 2017, 29, 165–172. [Google Scholar] [CrossRef] [PubMed]
- Porreca, A.; Noale, M.; Artibani, W.; Bassi, P.F.; Bertoni, F.; Bracarda, S.; Conti, G.N.; Corvò, R.; Gacci, M.; Graziotti, P.; et al. Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study. Health Qual. Life Outcomes 2018, 16, 122. [Google Scholar] [CrossRef] [PubMed]
- Epstein, J.I.; Egevad, L.; Amin, M.B.; Delahunt, B.; Srigley, J.R.; Humphrey, P.A. The 2014 international society of urological pathology (ISUP) consensus conference on gleason grading of prostatic carcinoma: Definition of grading patterns and proposal for a new grading system. Am. J. Surg. Pathol. 2016, 40, 244–252. [Google Scholar] [CrossRef] [PubMed]
- Irani, J.; Levillain, P.; Goujon, J.M.; Bon, D.; Dore, B.; Aubert, J. Inflammation in benign prostatic hyperplasia: Correlation with prostate specific antigen value. J. Urol. 1997, 157, 1301–1303. [Google Scholar] [CrossRef]
- Nickel, J.C.; Roehrborn, C.G.; O’Leary, M.P.; Bostwick, D.G.; Somerville, M.C.; Rittmaster, R.S. The relationship between prostate inflammation and lower urinary tract symptoms: Examination of baseline data from the REDUCE trial. Eur. Urol. 2008, 54, 1379–1384. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schatteman, P.H.; Hoekx, L.; Wyndaele, J.J.; Jeuris, W.; Van Marck, E. Inflammation in prostate biopsies of men without prostatic malignancy or clinical prostatitis: Correlation with total serum PSA and PSA density. Eur. Urol. 2000, 37, 404–412. [Google Scholar] [CrossRef] [PubMed]
- Sfanos, K.S.; De Marzo, A.M. Prostate cancer and inflammation: The evidence. Histopathology 2012, 60, 199–215. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tafuri, A.; Sebben, M.; Novella, G.; Pirozzi, M.; Processali, T.; Shakir, A.; Rizzetto, R.; Amigoni, N.; Bernasconi, R.; Brunelli, M.; et al. Prostatic chronic inflammation and prostate cancer risk at baseline random biopsy: Analysis of predictors. Arab. J. Urol. 2020, 18, 148–154. [Google Scholar] [CrossRef] [PubMed]
- Dennis, L.K.; Lynch, C.F.; Torner, J.C. Epidemiologic association between prostatitis and prostate cancer. Urology 2002, 60, 78–83. [Google Scholar] [CrossRef] [PubMed]
- Sutcliffe, S.; Giovannucci, E.; De Marzo, A.M.; Leitzmann, M.F.; Willett, W.C.; Platz, E.A. Gonorrhea, syphilis, clinical prostatitis, and the risk of prostate cancer. Cancer Epidemiol. Biomark. Prev. 2006, 15, 2160–2166. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Miller, A.M.; Lundberg, K.; Ozenci, V.; Banham, A.H.; Hellström, M.; Egevad, L.; Pisa, P. CD4+CD25high T cells are enriched in the tumor and peripheral blood of prostate cancer patients. J. Immunol. 2006, 177, 7398–7405. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nguyen, D.P.; Li, J.; Yadav, S.S.; Tewari, A.K. Recent insights into NF-κB signalling pathways and the link between inflammation and prostate cancer. BJU Int. 2014, 114, 168–176. [Google Scholar] [CrossRef] [PubMed]
- Brawn, P.N.; Speights, V.O.; Kuhl, D.; Riggs, M.; Spiekerman, A.M.; McCord, R.G.; Coffield, K.S.; Stewart, D.T.; Lind, M.L. Prostate-specific antigen levels from completely sectioned, clinically benign, whole prostates. Cancer 1991, 68, 1592–1599. [Google Scholar] [CrossRef] [PubMed]
- Bare, R.; Hart, L.; McCullough, D.L. Correlation of prostate-specific antigen and prostate-specific antigen density with outcome of prostate biopsy. Urology 1994, 43, 191–196. [Google Scholar] [CrossRef] [PubMed]
- Nadler, R.B.; Humphrey, P.A.; Smith, D.S.; Catalona, W.J.; Ratliff, T.L. Effect of inflammation and benign prostatic hyperplasia on elevated serum prostate specific antigen levels. J. Urol. 1995, 154 Pt 1, 407–413. [Google Scholar] [CrossRef] [PubMed]
- True, L.D.; Berger, R.E.; Rothman, I.; Ross, S.O.; Krieger, J.N. Prostate histopathology and the chronic prostatitis/chronic pelvic pain syndrome: A prospective biopsy study. J. Urol. 1999, 162, 2014–2018. [Google Scholar] [CrossRef] [PubMed]
Patients (n = 197) | |
---|---|
Age at diagnosis, years, mean ± SD | 65.5 ± 7.5 |
Education > lower secondary school, n (%) | 154 (78.6) |
BMI, kg/m2, mean ± SD | 26.7 ± 3.2 |
Smoking status, current smoker, n (%) | 28 (14.3) |
Diabetes mellitus, n (%) | 20 (10.2) |
Family history of prostate cancer, n (%) | 48 (25.0) |
Family history of breast cancer, n (%) | 12 (7.9) |
Family history of ovarian cancer, n (%) | 4 (2.8) |
PSA at the diagnosis, ng/mL, median (Q1, Q3) | 6.7 (4.9, 9.8) |
Clinical T staging, n (%) | |
T1 | 123 (63.1) |
T2 | 65 (33.3) |
T3, T4 | 7 (3.6) |
Gleason Score at the diagnosis, n (%) | |
≤6 | 94 (47.7) |
3 + 4 | 53 (26.9) |
4 + 3 | 15 (7.6) |
≥8 | 35 (17.8) |
n = 749 | |
---|---|
Number of cores for each patient, mean ± SD | 11.3 ± 4.9 |
Positive cores for each patient, n, mean ± SD | 4.1 ± 2.9 |
Grade group, n (%) | |
1 | 276 (36.9) |
2 | 203 (27.1) |
3 | 81 (10.8) |
4 | 128 (17.1) |
5 | 61 (8.1) |
Gleason score, n (%) | |
3 + 3 | 280 (37.4) |
3 + 4 | 199 (26.6) |
3 + 5 | 2 (0.3) |
4 + 3 | 81 (10.8) |
4 + 4 | 80 (10.7) |
4 + 5 | 57 (7.6) |
5 + 3 | 5 (0.7) |
5 + 4 | 21 (2.8) |
5 + 5 | 24 (3.2) |
Risk, n (%) | |
Low | 280 (37.4) |
Intermediate | 280 (37.4) |
High | 189 (25.2) |
Neoplasia | No Neoplasia | p-Value | |
---|---|---|---|
(n = 749) | (n = 1471) | ||
Anatomical location, n (%) | 0.0031 | ||
Stromal | 351 (55.4) | 735 (63.5) | |
Periglandular | 244 (38.5) | 360 (31.1) | |
Glandular | 39 (6.2) | 62 (5.4) | |
Grade of inflammation, n (%) | 0.0004 | ||
Mild | 431 (68.0) | 884 (76.4) | |
Moderate | 187 (29.5) | 246 (21.3) | |
Severe | 16 (2.5) | 27 (2.3) | |
Extension of inflammatory infiltrates, n (%) | 0.0131 | ||
Focal (<10%) | 486 (76.8) | 936 (80.9) | |
Multifocal (10–50%) | 139 (22.0) | 195 (16.9) | |
Diffuse (>50%) | 8 (1.3) | 26 (2.3) | |
Inflammatory score, mean ± SD | 4.1 ± 1.3 | 3.9 ± 1.2 | 0.0001 |
Glandular Disruption, n (%) | 24 (3.5) | 27 (2.2) | 0.0821 |
Corpora Amilacea, n (%) | 210 (31.0) | 339 (27.5) | 0.1054 |
Chronic inflammation, n (%) | 634 (84.7) | 1157 (78.7) | 0.0007 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Sessa, F.; Nicoletti, R.; De Nunzio, C.; Porreca, A.; Magrini, S.M.; Mirone, V.; Tubaro, A.; Serni, S.; Gontero, P.; Noale, M.; et al. Inflammation and Prostate Cancer: Pathological Analysis from Pros-IT CNR 2. Cancers 2023, 15, 630. https://doi.org/10.3390/cancers15030630
Sessa F, Nicoletti R, De Nunzio C, Porreca A, Magrini SM, Mirone V, Tubaro A, Serni S, Gontero P, Noale M, et al. Inflammation and Prostate Cancer: Pathological Analysis from Pros-IT CNR 2. Cancers. 2023; 15(3):630. https://doi.org/10.3390/cancers15030630
Chicago/Turabian StyleSessa, Francesco, Rossella Nicoletti, Cosimo De Nunzio, Angelo Porreca, Stefano Maria Magrini, Vincenzo Mirone, Andrea Tubaro, Sergio Serni, Paolo Gontero, Marianna Noale, and et al. 2023. "Inflammation and Prostate Cancer: Pathological Analysis from Pros-IT CNR 2" Cancers 15, no. 3: 630. https://doi.org/10.3390/cancers15030630