CONTEXT: Gastrointestinal stromal tumors (GISTs) are Kit/CD117-expressing mesenchymal neoplasms of uncertain malignant potential. The lack of a reliable method of prognostication hampers the selection of patients eligible for STI571 therapy. 10q22-q23 is a region involved in chromosomal losses found in a fraction of malignant primary and metastatic GISTs harboring PTEN (phosphatase and tensin homologue deleted on chromosome 10), a tumor suppressor gene often altered in human neoplasms. OBJECTIVE: To investigate the role of PTEN in GISTs, an issue that to our knowledge has not been addressed previously. DESIGN: PTEN status was determined in a series of 21 GISTs, with follow-up ranging between 6 and 198 months, using immunohistochemistry correlated with clinical data. RESULTS: A greater than 25% fraction of cells with low or absent PTEN immunostaining was detected in 9 GISTs, including all those showing malignancy. By the log-rank test, a fraction of PTEN-deficient cells greater than 25% was associated with malignancy (P <.001). Percentage of cells underexpressing PTEN, size, cellularity, MIB-1 immunoreactivity, and coagulative necrosis proved to be associated with malignancy by Cox proportional hazards univariate analysis; low or absent expression of PTEN was the only factor selected by multivariate analysis (P =.03). CONCLUSIONS: PTEN downregulation is implied in GIST progression. The immunohistochemical assessment of PTEN status appears to be a promising method of GIST prognostication.
CONTEXT: Gastrointestinal stromal tumors (GISTs) are Kit/CD117-expressing mesenchymal neoplasms of uncertain malignant potential. The lack of a reliable method of prognostication hampers the selection of patients eligible for STI571 therapy. 10q22-q23 is a region involved in chromosomal losses found in a fraction of malignant primary and metastatic GISTs harboring PTEN (phosphatase and tensin homologue deleted on chromosome 10), a tumor suppressor gene often altered in humanneoplasms. OBJECTIVE: To investigate the role of PTEN in GISTs, an issue that to our knowledge has not been addressed previously. DESIGN:PTEN status was determined in a series of 21 GISTs, with follow-up ranging between 6 and 198 months, using immunohistochemistry correlated with clinical data. RESULTS: A greater than 25% fraction of cells with low or absent PTEN immunostaining was detected in 9 GISTs, including all those showing malignancy. By the log-rank test, a fraction of PTEN-deficient cells greater than 25% was associated with malignancy (P <.001). Percentage of cells underexpressing PTEN, size, cellularity, MIB-1 immunoreactivity, and coagulative necrosis proved to be associated with malignancy by Cox proportional hazards univariate analysis; low or absent expression of PTEN was the only factor selected by multivariate analysis (P =.03). CONCLUSIONS:PTEN downregulation is implied in GIST progression. The immunohistochemical assessment of PTEN status appears to be a promising method of GIST prognostication.
Authors: Giuseppe Floris; Agnieszka Wozniak; Raf Sciot; Haifu Li; Lori Friedman; Thomas Van Looy; Jasmien Wellens; Peter Vermaelen; Christophe M Deroose; Jonathan A Fletcher; Maria Debiec-Rychter; Patrick Schöffski Journal: Clin Cancer Res Date: 2012-12-11 Impact factor: 12.531
Authors: Dolores Di Vizio; Francesca Demichelis; Sara Simonetti; Guido Pettinato; Luigi Terracciano; Luigi Tornillo; Michael R Freeman; Luigi Insabato Journal: BMC Cancer Date: 2008-05-13 Impact factor: 4.430