Time-dependent biological differences in molecular markers of high-grade urothelial cancer over 7 decades (ras proteins, pTEN, uPAR, PAI-1 and MMP-9).

The aim of this study was to evaluate changes and correlations between various molecular markers related to growth regulation and invasiveness in urothelial carcinomas in samples collected from 1932 to 2004. Paraffin-embedded autopsy/biopsy tissues from 144 patients were stained with antibodies agai...

Descripción completa

Detalles Bibliográficos
Publicado en:Virchows Archiv: European Journal of Pathology Vol. 461; no. 5; pp. 541 - 552
Autores principales: Litlekalsoy J, Hostmark JG, Costea DE, Illemann M, Laerum OD, Litlekalsoy, Jorunn, Hostmark, Jens G, Costea, Daniela Elena, Illemann, Martin, Laerum, Ole Didrik
Formato: research Journal Article
Publicado: Springer Nature Nov2012
Acceso en línea:Ver este registro en EBSCOhost
fields @attributes:
  recordID: 1
pdfLink:
plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104383881&site=ehost-live
header:
  @attributes:
    shortDbName: ccm
    uiTerm: 104383881
    longDbName: CINAHL Complete
    uiTag: AN
  controlInfo:
    bkinfo:
    dissinfo:
    jinfo:
      jid:
        09456317
        O1Z
      jtl: Virchows Archiv: European Journal of Pathology
      issn: 09456317
      maglogo: N
    pubinfo:
      dt: Nov2012
      vid: 461
      iid: 5
      pid: 237
      pub: Springer Nature
      place: New York, New York
    artinfo:
      ui:
        104383881
        NLM23052373
        2011754915
        10.1007/s00428-012-1323-y
        NLM23052373
        104383881
      ppf: 541
      ppct: 11
      formats:
        fmt:
          @attributes:
            type: P
      tig:
        atl: Time-dependent biological differences in molecular markers of high-grade urothelial cancer over 7 decades (ras proteins, pTEN, uPAR, PAI-1 and MMP-9).
      aug:
        au:
          Litlekalsoy J
          Hostmark JG
          Costea DE
          Illemann M
          Laerum OD
          Litlekalsoy, Jorunn
          Hostmark, Jens G
          Costea, Daniela Elena
          Illemann, Martin
          Laerum, Ole Didrik
        affil: The Gade Institute, Section for Pathology, University of Bergen, 5021 Bergen, Norway
      sug:
        subj:
          Carcinoma, Transitional Cell Metabolism
          Proteins Metabolism
          Tumor Markers, Biological Metabolism
          Urologic Neoplasms Metabolism
          Aged
          Carcinoma, Transitional Cell Pathology
          Female
          Human
          Immunohistochemistry
          In Situ Hybridization
          Male
          Peptide Hydrolases Metabolism
          Glycoproteins Metabolism
          Phosphatases Metabolism
          Blood Coagulation Factors Metabolism
          Receptors, Cell Surface Metabolism
          Time Factors
          Urologic Neoplasms Pathology
          Aged: 65+ years
          Female
          Male
      ab: The aim of this study was to evaluate changes and correlations between various molecular markers related to growth regulation and invasiveness in urothelial carcinomas in samples collected from 1932 to 2004. Paraffin-embedded autopsy/biopsy tissues from 144 patients were stained with antibodies against H-K-N ras proteins, pTEN protein, urokinase plasminogen activator receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1) and matrix metalloproteinase-9 (MMP-9) and analyzed by in situ hybridization. Statistical analysis was performed by SPSS using cross tabulation and logistic regression. While the presence of K-ras, N-ras, PAI-1, and loss of pTEN increased over the last few decades, uPAR expression decreased during the same period. The increase in K-ras expression associated positively with the increase in expression of the other two ras proteins, H-ras and N-ras, and the loss of pTEN. A strong positive correlation was also observed between PAI-1 and uPAR, PAI-1 and previously detected markers, EGFR (epidermal growth factor receptor) and p53. Presence of uPAR was found to be positively associated with p16 expression. Multivariate analysis with clinical parameters revealed a positive correlation between PAI-1 expression and tumour grade, CkHMW (high molecular weight cytokeratin) and tumour grade, CkHMW and metastasis, EGFR and metastasis. mRNA could be detected in samples from the last 50 years while older samples were negative, indicating its complete degradation during longer storage. In conclusion, increased accumulation of K-ras, N-ras, and PAI-1 together with loss of pTEN in bladder carcinomas of grades II and III seems to be more dominant in recent times, suggesting an altered malignant potential in these neoplasms.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
    refInfo:
    holdings:
      @attributes:
        islocal: N