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AIM: To elucidate the prognostic role and relationship of three molecular markers such as tumor suppressor gene p53, proliferating cell nuclear antigen (PCNA) and Ki-67 in gastric stromal tumor.METHODS: A total of 108 surgically resected gastric smooth muscle tumor specimens were collected from January 1987 to December 1999. Immunohistochemical studies were performed on the paraffin sections of 99 of 108 CD117-positive tumors with antibodies of p53,PCNA, and Ki-67. Immunoreactivity of three molecular markers was recorded by labeling index (LI, %) and was analyzed for clinicopathologic and survival correlation.RESULTS: Of the 99 cases, immunostaining revealed that 52 patients (52.5%) had p53, and 37 patients (37.3%) had Ki-67 immunoreactivity (defined as ＞10% of LI). All patients (100%) had PCNA immunoreactivity ranging from 12% to 93% of LI, divided into high or low by median. Statistics revealed that LI of three markers positively correlate to each other (P＜0.01) and to microscopic tumor mitotic counts (P＜0.001).By combination, patients with ≥2 markers (positive or high) in tumors had early tumor recurrence (P＜0.001) and unfavorable outcome (P＜0.001).Univariate analysis indicated that patients with tumor size ＞5 cm (P=0.003), tumor mitosis ＞5/50 HPF (P＜ 0.001), p53 immunoreactivity (P= 0.001), Ki-67 immunoreactivity (P=0.026), high PCNA LI (P=0.015) and male gender (P=0.036) were six predictors for early disease recurrence. Subsequent multivariate analysis revealed that mitotic counts, tumor size, and p53 immunoreactivity were three independent prognostic factors for both disease free and overall survival of patients. By combination of three independent prognostic factors for grouping, we found higher tumor recurrence rate (P＜0.001) and shorter survival (P＜0.001) existed in groups with increasing factors.CONCLUSION: We first provide the prognostic value and linkage of three molecular markers in GISTs. The combination of three factors (p53, tumor size, and tumor mitosis) provides a more powerful prediction of prognosis than any single factor does.