Prostate-specific membrane antigen and fibroblast activation protein distribution in prostate cancer: preliminary data on immunohistochemistry and PET imaging.
FAP
Fibroblast activation protein
PSMA
Prostate cancer
Journal
Annals of nuclear medicine
ISSN: 1864-6433
Titre abrégé: Ann Nucl Med
Pays: Japan
ID NLM: 8913398
Informations de publication
Date de publication:
Mar 2022
Mar 2022
Historique:
received:
11
08
2021
accepted:
24
11
2021
pubmed:
3
12
2021
medline:
5
4
2022
entrez:
2
12
2021
Statut:
ppublish
Résumé
Fibroblast activation protein (FAP) has been recently presented as new imaging target for malignant diseases and offers high contrast to surrounding normal tissue. FAP tracer uptake has been reported in various tumor entities. The aim of this study was to compare FAP and Prostate-specific membrane antigen (PSMA) expression in primary prostate cancer employing histological analyses and PET imaging in two small patient collectives. Two independent small patient collectives were included in this study. For cohort A, data of 5 prostate cancer patients and 3 patients with benign prostate hyperplasia were included. Patients with prostate cancer were initially referred for PSMA PET staging. Radical prostatectomy was performed in all patients and prostate specimen of patients and biopsies of healthy controls were available for further evaluation. Histological workup included HE and immunohistochemistry using PSMA Ab, FAP Ab. Cohort B consists of 6 Patients with diagnosed mCRPC and available PSMA as well as FAP PET. Patients with proven prostate cancer infiltration exhibited strong positivity for PSMA in both primary tumors and lymph node metastases while stainings for FAP were found positive in some cases, but not all (2/5). Controls with BPH presented moderate PSMA staining and in one case also with a positive FAP staining (1/3). PET imaging with FAP seemed to result in more precise results in case of low PSMA expression than PSMA-PET. While PSMA staining intensity is a valid indicator of prostate cancer in both primary tumor and lymph node metastases, the expression of FAP seems to be heterogeneous but not necessarily linked to cancer-associated fibroblasts. It is also present in inflammation-associated myofibroblasts. Therefore, its ultimate role in prostate cancer diagnosis remains a subject of discussion.
Identifiants
pubmed: 34854061
doi: 10.1007/s12149-021-01702-8
pii: 10.1007/s12149-021-01702-8
pmc: PMC8897381
doi:
Substances chimiques
Gallium Radioisotopes
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
293-301Informations de copyright
© 2021. The Author(s).
Références
Chen X, Song E. Turning foes to friends: targeting cancer-associated fibroblasts. Nat Rev Drug Discov. 2019;18:99–115. https://doi.org/10.1038/s41573-018-0004-1 .
doi: 10.1038/s41573-018-0004-1
pubmed: 30470818
Liu F, Qi L, Liu B, Liu J, Zhang H, Che D, et al. Fibroblast activation protein overexpression and clinical implications in solid tumors: a meta-analysis. PLoS ONE. 2015;10: e0116683. https://doi.org/10.1371/journal.pone.0116683 .
doi: 10.1371/journal.pone.0116683
pubmed: 25775399
pmcid: 4361589
Giesel FL, Kratochwil C, Lindner T, Marschalek MM, Loktev A, Lehnert W, et al. (68)Ga-FAPI PET/CT: biodistribution and preliminary dosimetry estimate of 2 DOTA-containing FAP-targeting agents in patients with various cancers. J Nucl Med. 2019;60:386–92. https://doi.org/10.2967/jnumed.118.215913 .
doi: 10.2967/jnumed.118.215913
pubmed: 30072500
pmcid: 30072500
Niedermeyer J, Garin-Chesa P, Kriz M, Hilberg F, Mueller E, Bamberger U, et al. Expression of the fibroblast activation protein during mouse embryo development. Int J Dev Biol. 2001;45:445–7.
pubmed: 11330865
Jacob M, Chang L, Pure E. Fibroblast activation protein in remodeling tissues. Curr Mol Med. 2012;12:1220–43. https://doi.org/10.2174/156652412803833607 .
doi: 10.2174/156652412803833607
pubmed: 22834826
Brennen WN, Isaacs JT, Denmeade SR. Rationale behind targeting fibroblast activation protein-expressing carcinoma-associated fibroblasts as a novel chemotherapeutic strategy. Mol Cancer Ther. 2012;11:257–66. https://doi.org/10.1158/1535-7163.MCT-11-0340 .
doi: 10.1158/1535-7163.MCT-11-0340
pubmed: 22323494
pmcid: 3586189
Kratochwil C, Flechsig P, Lindner T, Abderrahim L, Altmann A, Mier W, et al. (68)Ga-FAPI PET/CT: tracer uptake in 28 different kinds of cancer. J Nucl Med. 2019;60:801–5. https://doi.org/10.2967/jnumed.119.227967 .
doi: 10.2967/jnumed.119.227967
pubmed: 30954939
pmcid: 30954939
Pure E, Blomberg R. Pro-tumorigenic roles of fibroblast activation protein in cancer: back to the basics. Oncogene. 2018;37:4343–57. https://doi.org/10.1038/s41388-018-0275-3 .
doi: 10.1038/s41388-018-0275-3
pubmed: 29720723
pmcid: 6092565
Koczorowska MM, Tholen S, Bucher F, Lutz L, Kizhakkedathu JN, De Wever O, et al. Fibroblast activation protein-alpha, a stromal cell surface protease, shapes key features of cancer associated fibroblasts through proteome and degradome alterations. Mol Oncol. 2016;10:40–58. https://doi.org/10.1016/j.molonc.2015.08.001 .
doi: 10.1016/j.molonc.2015.08.001
pubmed: 26304112
Wen X, He X, Jiao F, Wang C, Sun Y, Ren X, et al. Fibroblast activation protein-alpha-positive fibroblasts promote gastric cancer progression and resistance to immune checkpoint blockade. Oncol Res. 2017;25:629–40. https://doi.org/10.3727/096504016X14768383625385 .
doi: 10.3727/096504016X14768383625385
pubmed: 27983931
pmcid: 7841289
Lv B, Xie F, Zhao P, Ma X, Jiang WG, Yu J, et al. Promotion of cellular growth and motility is independent of enzymatic activity of fibroblast activation protein-alpha. Cancer Genom Proteom. 2016;13:201–8.
Lindner T, Loktev A, Altmann A, Giesel F, Kratochwil C, Debus J, et al. Development of quinoline-based theranostic ligands for the targeting of fibroblast activation protein. J Nucl Med. 2018;59:1415–22. https://doi.org/10.2967/jnumed.118.210443 .
doi: 10.2967/jnumed.118.210443
pubmed: 29626119
pmcid: 29626119
Loktev A, Lindner T, Burger EM, Altmann A, Giesel F, Kratochwil C, et al. Development of fibroblast activation protein-targeted radiotracers with improved tumor retention. J Nucl Med. 2019;60:1421–9. https://doi.org/10.2967/jnumed.118.224469 .
doi: 10.2967/jnumed.118.224469
pubmed: 30850501
pmcid: 30850501
Loktev A, Lindner T, Mier W, Debus J, Altmann A, Jager D, et al. A tumor-imaging method targeting cancer-associated fibroblasts. J Nucl Med. 2018;59:1423–9. https://doi.org/10.2967/jnumed.118.210435 .
doi: 10.2967/jnumed.118.210435
pubmed: 29626120
pmcid: 6126438
Pang Y, Huang H, Fu L, Zhao L, Chen H. 68Ga-FAPI PET/CT detects gastric signet-ring cell carcinoma in a patient previously treated for prostate cancer. Clin Nucl Med. 2020;45:632–5. https://doi.org/10.1097/RLU.0000000000003099 .
doi: 10.1097/RLU.0000000000003099
pubmed: 32453079
Chen H, Zhao L, Ruan D, Pang Y, Hao B, Dai Y, et al. Usefulness of [(68)Ga]Ga-DOTA-FAPI-04 PET/CT in patients presenting with inconclusive [(18)F]FDG PET/CT findings. Eur J Nucl Med Mol Imaging. 2020. https://doi.org/10.1007/s00259-020-04940-6 .
doi: 10.1007/s00259-020-04940-6
pubmed: 33244618
pmcid: 8113179
Cardinale J, Schafer M, Benesova M, Bauder-Wust U, Leotta K, Eder M, et al. Preclinical evaluation of (18)F-PSMA-1007, a new prostate-specific membrane antigen ligand for prostate cancer imaging. J Nucl Med. 2017;58:425–31. https://doi.org/10.2967/jnumed.116.181768 .
doi: 10.2967/jnumed.116.181768
pubmed: 27789722
Giesel FL, Hadaschik B, Cardinale J, Radtke J, Vinsensia M, Lehnert W, et al. F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients. Eur J Nucl Med Mol Imaging. 2017;44:678–88. https://doi.org/10.1007/s00259-016-3573-4 .
doi: 10.1007/s00259-016-3573-4
pubmed: 27889802
Rahbar K, Afshar-Oromieh A, Bogemann M, Wagner S, Schafers M, Stegger L, et al. (18)F-PSMA-1007 PET/CT at 60 and 120 minutes in patients with prostate cancer: biodistribution, tumour detection and activity kinetics. Eur J Nucl Med Mol Imaging. 2018;45:1329–34. https://doi.org/10.1007/s00259-018-3989-0 .
doi: 10.1007/s00259-018-3989-0
pubmed: 29541812
Rahbar K, Afshar-Oromieh A, Seifert R, Wagner S, Schafers M, Bogemann M, et al. Diagnostic performance of (18)F-PSMA-1007 PET/CT in patients with biochemical recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45:2055–61. https://doi.org/10.1007/s00259-018-4089-x .
doi: 10.1007/s00259-018-4089-x
pubmed: 30027419
pmcid: 6182394
Humphrey PA. Histopathology of prostate cancer. Cold Spring Harb Perspect Med. 2017. https://doi.org/10.1101/cshperspect.a030411 .
doi: 10.1101/cshperspect.a030411
pubmed: 28389514
pmcid: 5629988
Bauer S, Jendro MC, Wadle A, Kleber S, Stenner F, Dinser R, et al. Fibroblast activation protein is expressed by rheumatoid myofibroblast-like synoviocytes. Arthritis Res Ther. 2006;8:R171. https://doi.org/10.1186/ar2080 .
doi: 10.1186/ar2080
pubmed: 17105646
pmcid: 1794515
Nagaraju CK, Dries E, Popovic N, Singh AA, Haemers P, Roderick HL, et al. Global fibroblast activation throughout the left ventricle but localized fibrosis after myocardial infarction. Sci Rep. 2017;7:10801. https://doi.org/10.1038/s41598-017-09790-1 .
doi: 10.1038/s41598-017-09790-1
pubmed: 28883544
pmcid: 5589875
Aimes RT, Zijlstra A, Hooper JD, Ogbourne SM, Sit ML, Fuchs S, et al. Endothelial cell serine proteases expressed during vascular morphogenesis and angiogenesis. Thromb Haemost. 2003;89:561–72.
doi: 10.1055/s-0037-1613388
de UitteWillige S, Malfliet JJ, Janssen HL, Leebeek FW, Rijken DC. Increased N-terminal cleavage of alpha-2-antiplasmin in patients with liver cirrhosis. J Thromb Haemost. 2013. https://doi.org/10.1111/jth.12396 .
doi: 10.1111/jth.12396
Khreish F, Rosar F, Kratochwil C, Giesel FL, Haberkorn U, Ezziddin S. Positive FAPI-PET/CT in a metastatic castration-resistant prostate cancer patient with PSMA-negative/FDG-positive disease. Eur J Nucl Med Mol Imaging. 2019. https://doi.org/10.1007/s00259-019-04623-x .
doi: 10.1007/s00259-019-04623-x
pubmed: 31814067
Isik EG, Has-Simsek D, Sanli O, Sanli Y, Kuyumcu S. Fibroblast activation protein-targeted PET imaging of metastatic castration-resistant prostate cancer compared with 68Ga-PSMA and 18F-FDG PET/CT. Clin Nucl Med. 2021. https://doi.org/10.1097/RLU.0000000000003837 .
doi: 10.1097/RLU.0000000000003837
pubmed: 34593693
Zhang Q, Peng C. Cancer-associated fibroblasts regulate the biological behavior of cancer cells and stroma in gastric cancer. Oncol Lett. 2018;15:691–8. https://doi.org/10.3892/ol.2017.7385 .
doi: 10.3892/ol.2017.7385
pubmed: 29399141
Goetz JG, Minguet S, Navarro-Lerida I, Lazcano JJ, Samaniego R, Calvo E, et al. Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis. Cell. 2011;146:148–63. https://doi.org/10.1016/j.cell.2011.05.040 .
doi: 10.1016/j.cell.2011.05.040
pubmed: 21729786
pmcid: 3244213
Yang TS, Yang XH, Chen X, Wang XD, Hua J, Zhou DL, et al. MicroRNA-106b in cancer-associated fibroblasts from gastric cancer promotes cell migration and invasion by targeting PTEN. FEBS Lett. 2014;588:2162–9. https://doi.org/10.1016/j.febslet.2014.04.050 .
doi: 10.1016/j.febslet.2014.04.050
pubmed: 24842611
He XJ, Tao HQ, Hu ZM, Ma YY, Xu J, Wang HJ, et al. Expression of galectin-1 in carcinoma-associated fibroblasts promotes gastric cancer cell invasion through upregulation of integrin beta1. Cancer Sci. 2014;105:1402–10. https://doi.org/10.1111/cas.12539 .
doi: 10.1111/cas.12539
pubmed: 25230369
pmcid: 4462364
Kesch C, Yirga L, Dendl K, Handke A, Darr C, Krafft U, et al. High fibroblast-activation-protein expression in castration-resistant prostate cancer supports the use of FAPI-molecular theranostics. Eur J Nucl Med Mol Imaging. 2021. https://doi.org/10.1007/s00259-021-05423-y .
doi: 10.1007/s00259-021-05423-y
pubmed: 34342669
pmcid: 8803688
Kessel K, Seifert R, Weckesser M, Roll W, Humberg V, Schlack K, et al. Molecular analysis of circulating tumor cells of metastatic castration-resistant prostate cancer patients receiving (177)Lu-PSMA-617 radioligand therapy. Theranostics. 2020;10:7645–55. https://doi.org/10.7150/thno.44556 .
doi: 10.7150/thno.44556
pubmed: 32685010
pmcid: 7359074
Saigusa S, Toiyama Y, Tanaka K, Yokoe T, Okugawa Y, Fujikawa H, et al. Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy. Int J Oncol. 2011;38:655–63. https://doi.org/10.3892/ijo.2011.906 .
doi: 10.3892/ijo.2011.906
pubmed: 21240461
Thang SP, Violet J, Sandhu S, Iravani A, Akhurst T, Kong G, et al. Poor outcomes for patients with metastatic castration-resistant prostate cancer with low prostate-specific membrane antigen (PSMA) expression deemed ineligible for (177)Lu-labelled PSMA radioligand therapy. Eur Urol Oncol. 2019;2:670–6. https://doi.org/10.1016/j.euo.2018.11.007 .
doi: 10.1016/j.euo.2018.11.007
pubmed: 31412006
Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. [Lu-177]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018;19:825–33. https://doi.org/10.1016/S1470-2045(18)30198-0 .
doi: 10.1016/S1470-2045(18)30198-0
Kessel K, Bernemann C, Bogemann M, Rahbar K. Evolving castration resistance and prostate specific membrane antigen expression: implications for patient management. Cancers (Basel). 2021. https://doi.org/10.3390/cancers13143556 .
doi: 10.3390/cancers13143556
Seifert R, Kessel K, Boegemann M, Kohler M, Roll W, Stegger L, et al. Additional local therapy for liver metastases in patients with metastatic castration-resistant prostate cancer receiving systemic PSMA-targeted therapy. J Nucl Med. 2020;61:723–8. https://doi.org/10.2967/jnumed.119.233429 .
doi: 10.2967/jnumed.119.233429
pubmed: 31601703