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.

Ricci, R., Arena, V., Castri, F., Martini, M., Maggiano, N. G., Murazio, M., Pacelli, F., Potenza, A., Vecchio, F. M., Larocca, L. M., Role of p16/INK4a in gastrointestinal stromal tumor progression, <<AMERICAN JOURNAL OF CLINICAL PATHOLOGY>>, 2004; 122 (1): 35-43. [doi:10.1309/MJ4X-N2M5-7HNC-8X5H] [http://hdl.handle.net/10807/27181]

Role of p16/INK4a in gastrointestinal stromal tumor progression

Ricci, Riccardo;Arena, Vincenzo;Castri, Federica;Martini, Maurizio;Maggiano, Nicola Giuseppe;Murazio, Marino;Pacelli, Fabio;Vecchio, Fabio Maria;Larocca, Luigi Maria
2004

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.
2004
Inglese
Ricci, R., Arena, V., Castri, F., Martini, M., Maggiano, N. G., Murazio, M., Pacelli, F., Potenza, A., Vecchio, F. M., Larocca, L. M., Role of p16/INK4a in gastrointestinal stromal tumor progression, <<AMERICAN JOURNAL OF CLINICAL PATHOLOGY>>, 2004; 122 (1): 35-43. [doi:10.1309/MJ4X-N2M5-7HNC-8X5H] [http://hdl.handle.net/10807/27181]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/27181
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