Abstract
Purpose
Prostate cancer (PCa) lacks specific markers capable of distinguishing aggressive tumors from those with indolent behavior. Therefore, the aim of this study was to evaluate the immunostaining of candidate proteins (PTEN, AKT, TRPM8, and NKX3.1) through the immunohistochemistry technique (IHC) on patients with metastatic and non-metastatic PCa.
Methods
Tissues from 60 patients were divided into three groups categorized according to prognostic parameters: better prognosis (n = 20), worse prognosis (n = 23), and metastatic (n = 17). Immunostaining was analyzed by a pathologist and staining classifications were considered according to signal intensity: (0) no staining, (+) weak, and (++ and +++) intermediate to strong.
Results
AKT protein was associated (p = 0.012) and correlated (p = 0.014; Tau = − 0.288) with the prognostic groups. The immunostaining for TRPM8 (p = 0.010) and NKX3.1 (p = 0.003) proteins differed between malignant tumor and non-tumoral adjacent tissue as well as for proteins in cellular locations (nucleus and cytoplasm). TRPM8 was independently associated with the ISUP grade ≥ 4 (p = 0.024; OR = 8.373; 95% CI = 1.319–53.164). The NKX3.1 showed positive and predominantly strong immunostaining in all patients in both tumoral and non-tumoral adjacent tissues. All metastatic samples had positive immunostaining, with strong intensity for NKX3.1 (p = 0.021; Tau = − 0.302). In the non-metastatic group, this strong protein staining was not observed in any patients.
Conclusion
This study confirmed that NKX3.1 is highly specific for prostate tissue and indicated that NKX3.1, AKT, and TRPM8 may be candidate markers for prostate cancer prognosis.
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Data availability
All data generated or analyzed during the current study are included in this published article.
Abbreviations
- WHO:
-
World Health Organization
- PCa:
-
Prostate cancer
- PSA:
-
Prostate-specific antigen
- IHC:
-
Immunohistochemistry
- PI3K:
-
Phosphatidylinositol-3-kinase
- AKT:
-
Serine/threonine kinase
- mTOR:
-
Mammalian target of the rapamycin complex
- TRPM8:
-
Transient receptor potential for melastatin 8
- NKX3.1:
-
NK3 homeobox 1
- HCL:
-
Londrina Cancer Hospital
- RP:
-
Radical prostatectomy
- TUR:
-
Transurethral resection
- NCCN:
-
National Comprehensive Cancer Network
- TNM:
-
Tumor/Node/Metastasis
- AJCC:
-
American Joint Committee on Cancer
- PBS:
-
Phosphate-buffered saline
- ISUP:
-
International Society of Urological Pathology
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Acknowledgements
All the authors would like to thank the Hospital do Câncer de Londrina and Angela Navarro Gordan for providing the samples for this study.
Funding
This study was supported by Fundação Araucária de Apoio ao Desenvolvimento Científico e Tecnológico do Paraná (Grant 185/2014), PPSUS (Grant 051/2021) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES—Finance Code 001). Pereira, E.R. received scholarship of CAPES and Cólus, I.M.S. received investigator fellowship awards from CNPq (Proc.308231/2017-1).
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ÉRP participated in the study design and acquisition of data, experimental procedures, performed the statistical analysis and interpretation, and drafted the manuscript. ALF and LCLP participated in the collection of samples and medical records, and also participated in the study design and immunohistochemical reactions. CAM participated in the study design and experimental procedures. AFMLG participated in the histopathological assays for the selection of tumor tissues and adjacent non-tumor tissues and performed the immunohistochemical analysis of the samples. KBdO participated in the statistical analysis and data interpretation. PEF made the sample collection possible. IMdSC participated in the design of the study and reviewed the manuscript for important intellectual content. RLG participated in the design of the study, interpretation of data, and gave final approval of the version to be published. All the authors read and approved the final manuscript.
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This study was approved by the Institutional Ethics Committee Involving Humans at State University of Londrina, Londrina—Paraná (PR), Brazil (CEP/UEL 176/2013; CAAE 19769913.0.0000.5231, in accordance with Resolution 466/12 of the National Research Ethics Commission).
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Pereira, É.R., Pinheiro, L.C.L., Francelino, A.L. et al. Tissue immunostaining of candidate prognostic proteins in metastatic and non-metastatic prostate cancer. J Cancer Res Clin Oncol 149, 567–577 (2023). https://doi.org/10.1007/s00432-022-04274-w
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DOI: https://doi.org/10.1007/s00432-022-04274-w