Segalés Tañà, Laura, 1994-Juanpere, NuriaGallarín, NereaLorenzo Perez, MartaLópez Martos, DavidPerera Bel, JúliaRodriguez-Vida, AlejoFumadó Ciutat, LluisCecchini Rosell, LluísBellmunt Molins, Joaquim, 1959-Lloreta, Josep, 1958-Hernández Llodrà, Silvia2024-02-052024-02-052024Segalés L, Juanpere N, Gallarín N, Lorenzo M, López D, Perera-Bel J, Rodriguez-Vida A, Fumadó L, Cecchini L, Bellmunt J, Lloreta-Trull J, Hernández-Llodrà S. Immunohistochemical markers as predictors of prognosis in multifocal prostate cancer. Virchows Arch. 2024 Aug;485(2):281-90. DOI: 10.1007/s00428-023-03699-z0945-6317http://hdl.handle.net/10230/58951The impact of tumor focality on prostate cancer (PCa) prognosis has been addressed in several studies with conflicting results. Tumor foci from multifocal (MF) PCa can show highly heterogeneous molecular features. Our aim was to analyze the protein expression of PTEN, SPOP, SLC45A3, ETV1, ERG and the "triple hit" (ERG overexpression, PTEN plus SLC45A3 loss) in unifocal (UF) and MF PCa, to evaluate their value as prognostic markers according to focality, and the role of tumor heterogeneity in MF disease. PTEN, SPOP, SLC45A3, ETV1 and ERG immunohistochemical expression was evaluated in 185 PCa from 9 TMAs, 51 UF and 134 MF. In a subset of 69 MF cases, the dominant and secondary foci (DF and SF) were compared. Heterogeneity was considered when both tumor foci presented different expression patterns. Relationship with clinicopathological features was also analyzed. MF PCa was diagnosed in significantly younger patients when compared to UF ones (p = 0.007). ETV1 overexpression was associated with UF disease (p = 0.028). A shorter time to PSA recurrence was related to SLC45A3 wt expression in UF PCa (p = 0.052), and to SPOP expression loss (p = 0.043) or "triple hit" phenotype in MF PCa (p = 0.041). In MF cases, PTEN loss, SLC45A3 loss and "triple hit" phenotype were associated with the DF and had significant heterogeneity. In conclusion, our results indicate that UF and MF PCa have relevant and consistent molecular differences. The analysis of an immunohistochemical panel, composed by PTEN, SPOP, SLC45A3, ETV1 and ERG, could be useful to predict outcome in MF cases.application/pdfeng© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1007/s00428-023-03699-zFocalityHeterogeneityImmunohistochemical panelPrognosisProstate cancerinfo:eu-repo/semantics/openAccess