Role of p16/INK4a in gastrointestinal stromal tumor progression

Riccardo Ricci, Vincenzo Arena, Maurizio Martini, Marino Murazio, Fabio Pacelli, Luigi Maria Larocca, Federica Castri, Nicola Giuseppe Maggiano, Fabio Maria Vecchio, Angelo Potenza

Risultato della ricerca: Contributo in rivistaArticolo in rivista

54 Citazioni (Scopus)

Abstract

Because the p16 locus is involved consistently in chromosomal losses found in malignant gastrointestinal stromal tumors (GISTs), we studied p16 in a series of 21 GISTs with complete follow-up using immunohistochemical analysis, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP). A fraction of cells of more than 20% with low or absent p16 immunostaining was detected in 12 GISTs, including all showing malignancy. RT-PCR revealed decreased p16 transcription in all except 2 p16 protein-deficient GISTs. By MSP, 7 cases showed p16 promoter methylation (all hypoexpressing p16; 6 malignant). A fraction of p16-deficient cells of more than 20% was associated with clinical malignancy (P = .003; log-rank test). The percentage of cells underexpressing p16, size, cellularity, mitotic count, and coagulative necrosis were associated with malignancy by Cox proportional hazards univariate analysis; only the former factor was selected by multivariate analysis (P = .039). Thus, p16 down-regulation, partly due to p16 promoter methylation, is implied in GIST progression. Furthermore, p16 immunohistochemical assessment seems a promising method for GIST prognostication.
Lingua originaleEnglish
pagine (da-a)35-43
Numero di pagine9
RivistaAmerican Journal of Clinical Pathology
Volume122
DOI
Stato di pubblicazionePubblicato - 2004

Keywords

  • Aged
  • Aged, 80 and over
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA Methylation
  • Disease Progression
  • Female
  • Gastrointestinal Neoplasms
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells
  • Tumor Markers, Biological

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