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17.02.2018 | Preclinical study

Prostate-specific membrane antigen in breast cancer: a comprehensive evaluation of expression and a case report of radionuclide therapy

verfasst von: Yuri Tolkach, Heidrun Gevensleben, Ralph Bundschuh, Aydan Koyun, Daniela Huber, Christina Kehrer, Thomas Hecking, Mignon-Denise Keyver-Paik, Christina Kaiser, Hojjat Ahmadzadehfar, Markus Essler, Walther Kuhn, Glen Kristiansen

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2018

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Abstract

Purpose

Prostate-specific membrane antigen (PSMA), a protein product of the folate hydrolase 1 (FOLH1) gene, is gaining increasing acceptance as a target for positron emission tomography/computer tomography (PET/CT) imaging in patients with several cancer types, including breast cancer. So far, PSMA expression in breast cancer endothelia has not been sufficiently characterized.

Methods

This study comprised 315 cases of invasive carcinoma of no special type (NST) and lobular breast cancer (median follow-up time 9.0 years). PSMA expression on tumor endothelia was detected by immunohistochemistry. Further, vascular mRNA expression of the FOLH1 gene (PSMA) was investigated in a cohort of patients with invasive breast cancer provided by The Cancer Genome Atlas (TCGA).

Results

Sixty percent of breast cancer cases exhibited PSMA-positive endothelia with higher expression rates in tumors of higher grade, NST subtype with Her2-positivity, and lack of hormone receptors. These findings were confirmed on mRNA expression levels. The highest PSMA rates were observed in triple-negative carcinomas (4.5 × higher than in other tumors). Further, a case of a patient with metastatic breast cancer showing PSMA expression in PET/CT imaging and undergoing PSMA radionuclide therapy is discussed in detail.

Conclusions

This study provides a rationale for the further development of PSMA-targeted imaging in breast cancer, especially in triple-negative tumors.

Spatz S, Tolkach Y, Jung K et al (2017) Comprehensive evaluation of prostate specific membrane antigen expression in the vasculature of renal tumors: implications for imaging studies and prognostic role. J Urol. https://doi.org/10.1016/j.juro.2017.08.079 PubMedCrossRef

Lütje S, Gomez B, Cohnen J et al (2017) Imaging of prostate-specific membrane antigen expression in metastatic differentiated thyroid cancer using 68 Ga-HBED-CC-PSMA PET/CT. Clin Nucl Med 42:20–25. https://doi.org/10.1097/RLU.0000000000001454 CrossRefPubMed

Hangaard L, Jochumsen MR, Vendelbo MH, Bouchelouche K (2017) Metastases from colorectal cancer avid on 68 Ga-PSMA PET/CT. Clin Nucl Med 42:532–533. https://doi.org/10.1097/RLU.0000000000001700 CrossRefPubMed

Haffner MC, Laimer J, Chaux A et al (2012) High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity. Mod Pathol 25:1079–1085. https://doi.org/10.1038/modpathol.2012.66 CrossRefPubMed

Haffner MC, Kronberger IE, Ross JS et al (2009) Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers. Hum Pathol 40:1754–1761. https://doi.org/10.1016/j.humpath.2009.06.003 CrossRefPubMed

Wernicke AG, Varma S, Greenwood EA et al (2014) Prostate-specific membrane antigen expression in tumor-associated vasculature of breast cancers. APMIS 122:482–489. https://doi.org/10.1111/apm.12195 CrossRefPubMed

Nomura N, Pastorino S, Jiang P et al (2014) Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases. Cancer Cell Int 14:26. https://doi.org/10.1186/1475-2867-14-26 CrossRefPubMedPubMedCentral

Chang SS, Reuter VE, Heston WD et al (1999) Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. Cancer Res 59:3192–3198PubMed

Sawicki LM, Buchbender C, Boos J et al (2017) Diagnostic potential of PET/CT using a 68 Ga-labelled prostate-specific membrane antigen ligand in whole-body staging of renal cell carcinoma: initial experience. Eur J Nucl Med Mol Imaging 44:102–107. https://doi.org/10.1007/s00259-016-3360-2 CrossRefPubMed

10.

Sathekge M, Lengana T, Modiselle M et al (2017) 68 Ga-PSMA-HBED-CC PET imaging in breast carcinoma patients. Eur J Nucl Med Mol Imaging 44:689–694. https://doi.org/10.1007/s00259-016-3563-6 CrossRefPubMed

11.

Kinoshita Y, Kuratsukuri K, Landas S et al (2006) Expression of prostate-specific membrane antigen in normal and malignant human tissues. World J Surg 30:628–636. https://doi.org/10.1007/s00268-005-0544-5 CrossRefPubMed

12.

Nguyen DP, Xiong PL, Liu H et al (2016) Induction of PSMA and internalization of an anti-PSMA mAb in the vascular compartment. Mol Cancer Res 14:1045–1053. https://doi.org/10.1158/1541-7786.MCR-16-0193 CrossRefPubMed

13.

Milowsky MI, Nanus DM, Kostakoglu L et al (2007) Vascular targeted therapy with anti–prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors. J Clin Oncol 25:540–547. https://doi.org/10.1200/JCO.2006.07.8097 CrossRefPubMed

14.

Meller B, Bremmer F, Sahlmann CO et al (2015) Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy. EJNMMI Res 5:66. https://doi.org/10.1186/s13550-015-0145-8 CrossRefPubMedPubMedCentral

15.

Murga JD, Moorji SM, Han AQ et al (2015) Synergistic co-targeting of prostate-specific membrane antigen and androgen receptor in prostate cancer. Prostate 75:242–254. https://doi.org/10.1002/pros.22910 CrossRefPubMed

16.

Sathekge M, Modiselle M, Vorster M et al (2015) ⁶⁸Ga-PSMA imaging of metastatic breast cancer. Eur J Nucl Med Mol Imaging 42:1482–1483. https://doi.org/10.1007/s00259-015-3066-x CrossRefPubMed

17.

Bühler P, Wolf P, Elsässer-Beile U (2009) Targeting the prostate-specific membrane antigen for prostate cancer therapy. Immunotherapy 1:471–481. https://doi.org/10.2217/imt.09.17 CrossRefPubMed

18.

Tykvart J, Navrátil V, Sedlák F et al (2014) Comparative analysis of monoclonal antibodies against prostate-specific membrane antigen (PSMA). Prostate 74:1674–1690. https://doi.org/10.1002/pros.22887 CrossRefPubMed

19.

Sasikumar A, Joy A, Nair BP et al (2017) False positive uptake in bilateral gynecomastia on 68 Ga-PSMA PET/CT Scan. Clin Nucl Med 42:e412–e414. https://doi.org/10.1097/RLU.0000000000001742 CrossRefPubMed

20.

Malik D, Basher RK, Mittal BR et al (2017) 68 Ga-PSMA expression in pseudoangiomatous stromal hyperplasia of the breast. Clin Nucl Med 42:58–60. https://doi.org/10.1097/RLU.0000000000001445 CrossRefPubMed

21.

Gordon IO, Tretiakova MS, Noffsinger AE et al (2008) Prostate-specific membrane antigen expression in regeneration and repair. Mod Pathol 21:1421–1427. https://doi.org/10.1038/modpathol.2008.143 CrossRefPubMed

22.

Ardies PJ, Gykiere P, Goethals L et al (2017) PSMA uptake in mediastinal sarcoidosis. Clin Nucl Med 42:303–305. https://doi.org/10.1097/RLU.0000000000001543 CrossRefPubMed

Titel: Prostate-specific membrane antigen in breast cancer: a comprehensive evaluation of expression and a case report of radionuclide therapy
verfasst von: Yuri Tolkach
Heidrun Gevensleben
Ralph Bundschuh
Aydan Koyun
Daniela Huber
Christina Kehrer
Thomas Hecking
Mignon-Denise Keyver-Paik
Christina Kaiser
Hojjat Ahmadzadehfar
Markus Essler
Walther Kuhn
Glen Kristiansen
Publikationsdatum: 17.02.2018
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2018
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-018-4717-y

Springer Medizin

Prostate-specific membrane antigen in breast cancer: a comprehensive evaluation of expression and a case report of radionuclide therapy