Niels J Rupp, Sandra N Freiberger, Daniela A Ferraro, Riccardo Laudicella, Jakob Heimer, Urs J Muehlematter, Cédric Poyet, Holger Moch, Daniel Eberli, Jan H Rüschoff, Irene A Burger
{"title":"免疫组化ERG阳性与原发性前列腺癌PSMA表达减少和相应的[68Ga]Ga-PSMA-11 PET扫描能见度降低有关。","authors":"Niels J Rupp, Sandra N Freiberger, Daniela A Ferraro, Riccardo Laudicella, Jakob Heimer, Urs J Muehlematter, Cédric Poyet, Holger Moch, Daniel Eberli, Jan H Rüschoff, Irene A Burger","doi":"10.1007/s00259-024-06856-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>TMPRSS2:ERG gene fusion negatively regulates PSMA expression in prostate adenocarcinoma (PCa) cell lines. Therefore, immunohistochemical (IHC) ERG expression, a surrogate for an underlying ERG rearrangement, and PSMA expression patterns in radical prostatectomy (RPE) specimens of primary PCa, including corresponding PSMA-PET scans were investigated.</p><p><strong>Methods: </strong>Two cohorts of RPE samples (total n=148): In cohort #1 (n=62 patients) with available RPE and preoperative [<sup>68</sup>Ga]Ga-PSMA-11 PET, WHO/ISUP grade groups, IHC-ERG (positive vs. negative) and IHC-PSMA expression (% PSMA-negative tumour area, PSMA<sub>%neg</sub>) were correlated with the corresponding SUV<sub>max</sub>. In the second cohort #2 (n=86 patients) including RPE only, same histopathological parameters were evaluated.</p><p><strong>Results: </strong>Cohort #1: PCa with IHC-ERG expression (35.5%) showed significantly lower IHC-PSMA expression and lower SUV<sub>max</sub> values on the corresponding PET scans. Eight of 9 PCa with negative PSMA-PET scans had IHC-ERG positivity, and confirmed TMPRSS2::ERG rearrangement. In IHC-PSMA positive PCa, IHC-ERG positivity was significantly associated with lower SUV<sub>max</sub> values. In cohort #2, findings of higher IHC-PSMA<sub>%neg</sub> and IHC-ERG expression was confirmed with only 0-10% PSMA<sub>%neg</sub> tumour areas in IHC-ERG-negative PCa.</p><p><strong>Conclusion: </strong>IHC-ERG expression is significantly associated with more heterogeneous and lower IHC-PSMA tissue expression in two independent RPE cohorts. There is a strong association of ERG positivity in RPE tissue with lower [<sup>68</sup>Ga]Ga-PSMA-11 uptake on corresponding PET scans. Results may serve as a base for future biomarker development to enable tumour-tailored, individualized imaging approaches.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"305-313"},"PeriodicalIF":8.6000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599624/pdf/","citationCount":"0","resultStr":"{\"title\":\"Immunohistochemical ERG positivity is associated with decreased PSMA expression and lower visibility in corresponding [<sup>68</sup>Ga]Ga-PSMA-11 PET scans of primary prostate cancer.\",\"authors\":\"Niels J Rupp, Sandra N Freiberger, Daniela A Ferraro, Riccardo Laudicella, Jakob Heimer, Urs J Muehlematter, Cédric Poyet, Holger Moch, Daniel Eberli, Jan H Rüschoff, Irene A Burger\",\"doi\":\"10.1007/s00259-024-06856-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>TMPRSS2:ERG gene fusion negatively regulates PSMA expression in prostate adenocarcinoma (PCa) cell lines. Therefore, immunohistochemical (IHC) ERG expression, a surrogate for an underlying ERG rearrangement, and PSMA expression patterns in radical prostatectomy (RPE) specimens of primary PCa, including corresponding PSMA-PET scans were investigated.</p><p><strong>Methods: </strong>Two cohorts of RPE samples (total n=148): In cohort #1 (n=62 patients) with available RPE and preoperative [<sup>68</sup>Ga]Ga-PSMA-11 PET, WHO/ISUP grade groups, IHC-ERG (positive vs. negative) and IHC-PSMA expression (% PSMA-negative tumour area, PSMA<sub>%neg</sub>) were correlated with the corresponding SUV<sub>max</sub>. In the second cohort #2 (n=86 patients) including RPE only, same histopathological parameters were evaluated.</p><p><strong>Results: </strong>Cohort #1: PCa with IHC-ERG expression (35.5%) showed significantly lower IHC-PSMA expression and lower SUV<sub>max</sub> values on the corresponding PET scans. Eight of 9 PCa with negative PSMA-PET scans had IHC-ERG positivity, and confirmed TMPRSS2::ERG rearrangement. In IHC-PSMA positive PCa, IHC-ERG positivity was significantly associated with lower SUV<sub>max</sub> values. In cohort #2, findings of higher IHC-PSMA<sub>%neg</sub> and IHC-ERG expression was confirmed with only 0-10% PSMA<sub>%neg</sub> tumour areas in IHC-ERG-negative PCa.</p><p><strong>Conclusion: </strong>IHC-ERG expression is significantly associated with more heterogeneous and lower IHC-PSMA tissue expression in two independent RPE cohorts. There is a strong association of ERG positivity in RPE tissue with lower [<sup>68</sup>Ga]Ga-PSMA-11 uptake on corresponding PET scans. Results may serve as a base for future biomarker development to enable tumour-tailored, individualized imaging approaches.</p>\",\"PeriodicalId\":11909,\"journal\":{\"name\":\"European Journal of Nuclear Medicine and Molecular Imaging\",\"volume\":\" \",\"pages\":\"305-313\"},\"PeriodicalIF\":8.6000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599624/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Nuclear Medicine and Molecular Imaging\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00259-024-06856-x\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/31 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Nuclear Medicine and Molecular Imaging","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00259-024-06856-x","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/31 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Immunohistochemical ERG positivity is associated with decreased PSMA expression and lower visibility in corresponding [68Ga]Ga-PSMA-11 PET scans of primary prostate cancer.
Purpose: TMPRSS2:ERG gene fusion negatively regulates PSMA expression in prostate adenocarcinoma (PCa) cell lines. Therefore, immunohistochemical (IHC) ERG expression, a surrogate for an underlying ERG rearrangement, and PSMA expression patterns in radical prostatectomy (RPE) specimens of primary PCa, including corresponding PSMA-PET scans were investigated.
Methods: Two cohorts of RPE samples (total n=148): In cohort #1 (n=62 patients) with available RPE and preoperative [68Ga]Ga-PSMA-11 PET, WHO/ISUP grade groups, IHC-ERG (positive vs. negative) and IHC-PSMA expression (% PSMA-negative tumour area, PSMA%neg) were correlated with the corresponding SUVmax. In the second cohort #2 (n=86 patients) including RPE only, same histopathological parameters were evaluated.
Results: Cohort #1: PCa with IHC-ERG expression (35.5%) showed significantly lower IHC-PSMA expression and lower SUVmax values on the corresponding PET scans. Eight of 9 PCa with negative PSMA-PET scans had IHC-ERG positivity, and confirmed TMPRSS2::ERG rearrangement. In IHC-PSMA positive PCa, IHC-ERG positivity was significantly associated with lower SUVmax values. In cohort #2, findings of higher IHC-PSMA%neg and IHC-ERG expression was confirmed with only 0-10% PSMA%neg tumour areas in IHC-ERG-negative PCa.
Conclusion: IHC-ERG expression is significantly associated with more heterogeneous and lower IHC-PSMA tissue expression in two independent RPE cohorts. There is a strong association of ERG positivity in RPE tissue with lower [68Ga]Ga-PSMA-11 uptake on corresponding PET scans. Results may serve as a base for future biomarker development to enable tumour-tailored, individualized imaging approaches.
期刊介绍：
The European Journal of Nuclear Medicine and Molecular Imaging serves as a platform for the exchange of clinical and scientific information within nuclear medicine and related professions. It welcomes international submissions from professionals involved in the functional, metabolic, and molecular investigation of diseases. The journal's coverage spans physics, dosimetry, radiation biology, radiochemistry, and pharmacy, providing high-quality peer review by experts in the field. Known for highly cited and downloaded articles, it ensures global visibility for research work and is part of the EJNMMI journal family.
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