Clinicopathologic study of primary malignant gastrointestinal stromal tumor of the stomach, with special reference to prognostic factors: Analysis of results in 140 surgically resected patients

Background. Malignant gastrointestinal stromal tumors (GISTs), previously termed leiomyosarcomas or epithelioid leiomyosarcomas, are known to show wide variability in their malignancy. We evaluated the clinicopathological features of a large number of primary malignant gastric GISTs to clarify which features were independent prognostic factors. Methods. Clinicopathologic features (age, sex, tumor location, mode of growth and size, surgical method, ulceration, cell type, nuclear atypia, cellularity, mitotic index, growth pattern, necrosis, hemorrhage, direct tumor invasion, peripheral lymphoid cuffing, expression of α-smooth muscle actin [α-SMA], desmin, caldesmon, vimentin, CD34, c-kit protein and S-100 protein, and MIB-1 index) were evaluated by multivariate analysis in 140 patients with resected primary malignant gastric GISTs to identify independent prognostic factors. Results. Univariate analysis showed that each of the following factors had a significant deleterious influence on prognosis: male sex, tumor size 10 cm or more, presence of ulceration, an epithelioid cell component, severe nuclear atypia, high cellularity, a mitotic index of more than 10, an exogastric or invasive growth pattern, necrosis, hemorrhage, direct tumor invasion of surrounding tissue, negative caldesmon immunoreactivity, positive S-100 protein immunoreactivity, and a MIB-1 antigen labeling index of more than 10%. Multivariate analysis showed that male sex, tumor size 10 cm or more, presence of an epithelioid cell component, and a mitotic index of more than 10 were statistically significant indicators of a poor prognosis (P = 0.013, 0.001, 0.014, and <0.001, respectively). Multivariate analysis using the MIB-1 index instead of a mitotic count showed that male sex, tumor size 10 cm or more, presence of necrosis, and a MIB-1 antigen labeling index of more than 10% were independent predictors of a poor prognosis (P = 0.009, 0.001, 0.043, and <0.001, respectively). Conclusion. Male sex, tumor size 10 cm or more, and cell proliferation as estimated by the mitotic index or MIB-1 index are independent indicators of a poor prognosis in primary malignant gastric GIST.