| Objective:To investigate the clinicopathological significance of expression of PTEN protein and Ki-67labeling index in primary gastrointestinal stromal tumors (GISTs) and their impacts on prognosis.Methods:Between January,2005and January,2011, a total of84patients with primary GISTs treated with operation in the Department of Gastrointestinal Surgery of the clinical medicine school of Yangzhou University. The clinical and pathological features were retrospectively analyzed based on follow-up data. Tumor samples and clinicopathological data from84patients with primary GISTs after R0resection and50adjacent normal gastrointestinal stromal tissues were obtained. Immunohistochemical analysis was performed based on tissue microarray (TMA) to estimate expression pattern of PTEN and Ki-67labeling index in tumor cells. Association of PTEN expression and Ki-67labeling index with clinicopathological features and relapse-free survival (RFS) were also analyzed.Results:The negative, weakly positive, positive, and strong positive expression rates of PTEN protein in GISTs group were13.1%,39.3%,44.0%and3.6%, respectively; while in the control group were8.0%,20.0%,40.0%, and32.0%, respectively, which was lower than those in control group (P<0.001). The average Ki-67labeling index was2.8%±4.3%(min1%, max23.3%) in GISTs group, which was significantly higher than that in the control group (0.8%±2.0%)(.P=0.004). The cut-off point of Ki-67labeling index was determined as1%by receiver operator characteristic (ROC) test with the area under the curve (AUC) of0.651, sensitivity of71.7%and specificity of64.5%, P=0.021. In our cohort, the5-year overall survival (OS) rate was93.1%;1-year,3-year and5-year RFS rate were98.8%,75.6%and59.5%, respectively. Univariate analysis demonstrated the following factors as poor prognostic indicators for RFS, gastrointestinal (GI) bleeding (P=0.009), non-gastric tumor location (P=0.001), large tumor size (P=0.022), high mitotic index (P<0.001), high cellularity (P=0.012), tumor rupture (P=0.013), absent or low expression of PTEN (P=0.036), and Ki-67LI>1%(P=0.043). GI bleeding [hazard ratio (HR)3.85,95%confidence interval (CI)1.63-9.10, P=0.002]was a negative independent risk predictor in multivariate analysis, in addition to tumor size (HR5.1-10cm vs.≤5cm=1.86,95%CI:0.67-5.15; HR>10cm vs.<5cm=6.71,95%CI:0.67-5.15; overall P=0.023), and mitotic index (HR5.1-10/50HPFs vs.≤5/50HPFs=5.72,95%CI:2.09-15.64; HR>10/50HPFs vs.≤5/50HPFs=3.44,95%CI:1.13-10.45; overall P=0.002). In addition, GI bleeding showed a good ability to predict recurrence potential, when included into our re-modified risk stratification criteria.Conclusions:This study suggests that the low expression of PTEN may be involved in the occurrence, development and poor prognostic of primary GISTs. Expression of PTEN and Ki-67are correlated with high risk potential and may predict early recurrence in univariate analysis. GI bleeding is an independent predictor of poor prognosis for RFS in primary GISTs. The evaluation of GI bleeding, primary site, tumor size, mitotic index, and tumor rupture may help predict the prognosis of GISTs. |
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