Refining Prognosis in Localized Gastrointestinal Stromal Tumor: Clinical Significance of Phosphatase and Tensin Homolog Low Expression and Gene Loss

To investigate the use of PTEN biomarker to improve prognostic stratification in patients with localized gastrointestinal stromal tumor (GIST). METHODS: PTEN expression and genomic analysis were performed on two independent GIST-60 (n = 60) and GIST-100 (n = 100) cohorts, respectively. RESULTS: PTEN expression was significantly lower in patients with local and metastatic recurrent tumor compared with those with no recurrence (P = .004). PTEN low expression was significantly associated with poor disease-free survival (DFS) compared with PTEN high expression (43.73 v 117.95 months; P = .0084) and distant metastatic-free survival (DMFS; 57.95 v 117.95 months; P = .0032). PTEN heterozygous loss was observed in approximately 10% of the patients in each cohort and was associated with poor DFS compared with patients with PTEN normal status (27.56 months v not reached [NR]; P < .001) and DMFS (27.56 months v NR; P < .001). Multivariate analysis revealed that PTEN expression was an independent clinical prognosis factor besides tumor size, mitosis index, and location (hazard ratio for DFS: 3.8; P = .033; hazard ratio for DMFS 5.7, P = .01). Furthermore, PTEN low expression was independently associated with poor DMFS in clinically high-risk patients (mDMFS: 42.28 v 65.61 months; P = .0166). In addition, PTEN heterozygous loss was independently associated with poor DMFS in patients at either low/intermediate risk (mDMFS: 18.05 months for PTEN loss v NR for PTEN normal status; P < .001) or at high risk (mDMFS: 27.19 months for PTEN loss v 105.36 months for PTEN normal status; P = .044). CONCLUSION: PTEN low expression/gene loss is an independent significant prognostic factor and a promising component to strengthen the clinical prognostic tools in patients with localized GIST.