Application And Evaluation Of NIH Grading Criteria For Localized Primary Gastrointestinal Stromal Tumors And Expression Of Dog1 And WISP-1 In Gastrointestinal Stromal Tumors And Their Clinic Significance

Objective To investigate the expression and clinical significance of Dogl and WISP-1 in gastrointestinal stromal tumors(GISTs), and to evaluate the prognostic significance of various clinicopathologic parameters and the implication of NIH(National Institutes of Health) grading criteria in gastrointestinal stromal tumors.Methods One hundred and twenty-four GISTs with complete clinicopathologic data were retrieved from the archival files of the Department of Pathology, Affiliated Hospital of North Sichuan Medical College. The clincal features, site of occurrence, tumour diameter, mitotic index were studied and analyzed statistically. The biologic potential by new-edited NIH grading criteria were evaluated. The expression levels of Dogl and WISP-1 were detected by immunohistochemistry in 124 cases of GIST tissues, and specimens from non-GISTs were used as controls.Results Of 124 GISTs,119(96%) were positive for Dog1 and 111 (91.0%) for CD 117. Dogl protein expression rate was significantly different between GISTs and non-GISTs (P< 0.001), but there were no significant differences between Dog1 and CD117 expression in GISTs. As for WISP-1, this antibody yielded positive staining in 100 of 124 (80.6%) GISTs. The expression rate of WISP-1 protein in very low risk, low risk, intermediate risk, and high risk cases was 44.4%(4/9),66.7%(26/39),86.9%(17/20),95.0% (38/40), and there was a significant correlation between WISP-1 protein expression and the risk score proposed by NIH(2008). Of all caes,13 were advanced (malignancy) GISTs and 111 were localized primary GISTs. The mean age of patients was 57 years. Follow-up information was available in 82 cases, of which 9 cases were advanced GISTs and 73 were localized primary GIST in which survival analyses were carried out. For the 73 localized primary GISTs, large tumour size(P=0.009), high mitotic index(P<0.001) was associated with lower survival. Statistical analysis showed that, with the largest tumour diameter of 5.1 to 10.0 cm, the nongastric GIST had lower disease-free survial(DFS) rate than gastric GIST (P=0.011). Survival rate had no correlation with age and sex. Evaluated by the new NIH(2008) grading criteria, the overall and disease-free survival rate of high risk GISTs was lower than that of very low risk, low risk, intermediate risk(P<0.05), whereas the overall and disease-free survival rate of very low risk, low risk, intermediate risk GISTs had no statistical differences. Conclusions Dogl was a sensitivity and specificity marker for GIST and should be used as "the first line" antibody as CD117 protein in routine diagnosis. The expression of WISP-1 maybe associated with GIST progression and could be used as a prognosis marker in GIST. Tumour size, location and mitotic index are the most important prognostic parameters in GISTs. The risk criteria for assessing the natural course of primary GISTs proposed by NIH(2008) were validated and indication of the NIH classification in the pathological diagnosis of GIST was beneficial to prognosis assessment of GIST as well as guidance on the clinical treatment of GIST.