Although the significance of various prognostic factors, such as tumor size and mitotic index (MI), has been well established for smooth-muscle tumors of the stomach, the significance of these factors in other sites is less well defined. We studied 1004 patients with gastrointestinal smooth-muscle tumors for whom vital status could be determined. The average MI and tumor size varied significantly among the five major sites examined: esophagus (53 cases), stomach (524 cases), small bowel 252 cases), colon/rectum (108 cases), and omentum/mesentery/peritoneum (67 cases). There was a significant difference in site-specific survival (p = 0.001), with 10-year survival varying between 50% and 70%. Multivariate analysis demonstrated tumor location (p = 0.0320), size (p = 0.0003), MI (p < 0.0001), and patient age (p < 0.0001) to each carry independent prognostic value. The significance of MI was highly site dependent. Separation of survival curves for the stomach, using a threshold for analysis of either 5 or 10 mitotic figures/50 high-power fields, was very good. In contrast, small-bowel tumors showed little separation between survival curves, regardless of whether a threshold of 1, 5, or 10 mitotic figures MF/50 high-power fields was used to distinguish groups. In no site were tumor size and MI alone sufficient to provide an accurate long-term prediction of prognosis. Although tumor location, size, MI, and age have independent value in predicting the prognosis of patients with gastrointestinal smooth-muscle tumors, better methods are still required to accurately predict clinical course.

To determine the prognostic impact of clinical, immunohistochemical, and biological parameters, we examined 52 gastrointestinal stromal tumors (GIST) by conventional light microscopy and immunohistochemistry. DNA ploidy was analyzed by image cytometry on cytospin preparation. The proliferative activity was determined by mitosis counting and assessment of Ki-67 reactivity by means of monoclonal antibody Ki-S5. A histopathologic grade was assigned to each tumor according to the French Federation of Cancer Centers (FNCLCC) grading system. Next to vimentin, CD34 was the most prevalent antigen, followed by markers of neural and muscular differentiation. Many tumors exhibited a mixed phenotype. Twenty-one tumors were diploid, eight hypodiploid, and 23 aneuploid. In univariate analysis, tumor grade, Ki-S5 labeling index, mitotic count, atypical mitoses, cellularity, and sex were predictive of both mortality and metastasis risk. DNA ploidy only correlated with overall survival, whereas the tumor location affected the occurrence of metastases. Multivariate analysis selected Ki-S5 scores (P < .0001) and atypical mitoses (P=.012) as independent prognosticators for overall survival, and tumor grade (P=.0036) and size (P=.0055) as predictors of metastatic spread. We conclude that GIST are primitive mesenchymal tumors capable of divergent differentiation, which does not influence their prognosis. The latter appears to be best predicted by histopathologic grading and the Ki-67 labeling index.

The DNA content and proliferative index of 61 gastrointestinal stromal tumors (GIST) were measured by image analysis and correlated with the lesion's clinicopathological features and patient's survival. DNA analysis was performed on cytospin single-cell preparations obtained from the paraffin-embedded tissue blocks. MIB-1 was the proliferation marker used on paraffin sections. DNA aneuploidy was detected in 12 tumors (18%), and high MIB-1 index (>22%) in 12 lesions (18%). DNA aneuploidy and high MIB-1 index statistically correlated with high mitotic rate (> or = 5 x 10 high-power field [HPF]) (P < .001) and with the presence of necrosis (P < .05). The patient's survival was significantly correlated with DNA ploidy (P < .01), MIB-1 index (P < .00001), mitotic rate (P < .00001), presence of necrosis (P < .0001), and size of the tumor (P < .01). Multivariate regression analysis showed that only MIB-1 index was an independent parameter in predicting the clinical outcome for patients with GIST. The mitotic rate was the only other independent prognostic factor when MIB-1 index was not allowed to enter the model.

To assess the prognostic value of DNA ploidy patterns, the DNA ploidy patterns of 37 primary gastrointestinal lymphomas were determined by DNA flow cytometry, using paraffin-embedded archival specimens. The DNA ploidy patterns were diploid in 21 tumors and nondiploid in 16 tumors. Advanced clinical stage, as determined by the Ann Arbor Staging Classification, and nondiploid DNA ploidy patterns were associated with significantly reduced survival of the patients, whereas tumor size, tumor grade, and the S-phase fraction of tumor cells were not correlated with survival. A multivariate analysis disclosed that the variables which had significant prognostic value for primary gastrointestinal lymphoma were the clinical stage of the disease and the DNA ploidy patterns of the tumor cells.