Nejvíce citovaný článek - PubMed ID 39907090
Contemporary review of prognostic markers of prostate cancer from a pathologist perspective
The tumor suppressor gene NKX3.1 and the LPL gene are located in close proximity on chromosome 8, and their deletion has been reported in multiple studies. However, the significance of LPL loss may be misinterpreted due to its co-deletion with NKX3.1, a well-established event in prostate carcinogenesis. This study investigates whether LPL deletion represents a biologically relevant event or occurs merely as a bystander to NKX3.1 loss. We analyzed 28 formalin-fixed paraffin-embedded prostate cancer samples with confirmed LPL deletion and 28 without. Immunohistochemical staining was performed, and previously published whole-genome sequencing data from 103 prostate cancer patients were reanalyzed. Deletion of the 8p21.3 region was associated with higher Gleason grade groups. While NKX3.1 expression was significantly reduced in prostate cancer compared to benign prostatic hyperplasia, LPL protein expression showed no significant difference between cancerous and benign tissue, nor was it affected by the 8p21.3 deletion status. Copy number analysis confirmed the co-deletion of NKX3.1 and LPL in 54 patients. Notably, NKX3.1 loss without accompanying LPL deletion was observed in eight additional cases. These findings suggest that LPL deletion is a passenger event secondary to NKX3.1 loss and underscore the importance of cautious interpretation of cytogenetic findings involving the LPL locus.
- Klíčová slova
- FISH, LPL, NKX3.1, immunohistochemistry, prostate cancer, whole-genome sequencing,
- MeSH
- delece genu * MeSH
- homeodoménové proteiny * genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prostaty * genetika patologie metabolismus MeSH
- progrese nemoci MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- transkripční faktory * genetika metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- homeodoménové proteiny * MeSH
- NKX3-1 protein, human MeSH Prohlížeč
- transkripční faktory * MeSH
Despite improving diagnostic possibilities, the incidence of prostate cancer is increasing, but we are not able to reduce the mortality rate. While PSA, 4K score, PCA3 and other urinary markers, ExoDX, SelectMDX, Confirm MDx or MiPS tests are used to identify potential prostate cancer carriers, Decipher, Prolaris or Oncotype DX tests are used to assess the aggressiveness of proven cancer in order to stratify patients for early or delayed treatment. More modern forms of treatment for advanced disease include second-generation antiandrogens and PARP inhibitors. By assessing genetic mutations (e.g. BRCA1, BRCA2 genes, single nucleotide polymorphism) or the presence of splice variants of the androgen receptor (ARV7), we are able to identify patients in whom the planned treatment may be expected to be ineffective and thus choose other treatment modalities. In the present review article, we offer a comprehensive overview of current diagnostic tests that find application in the diagnosis of early and advanced prostate cancer.
