To our knowledge, there has been no study assessing definitely prognostic values of EGFR in a large cohort of GISTs. However, no significant association was found between the EGFR expression and prognostic analysis of GISTs in our study. Increased COX-2 expression has been observed in colorectal adenoma and carcinoma[27]. The induction of COX-2 has been shown to promote cell growth, inhibit apoptosis and enhance cell motility and adhesion[28]. Over-expression of COX-2 has tumorigenic effects in animal models[29]. Expression levels of COX-2 and vascular endothelial growth factor were found to be significantly higher in malignant GISTs than those in benign and intermediate GISTs[30].

A study reported a correlation between the COX-2 expression and tumor cell proliferation in GISTs, but no association was found between COX-2 expression and mortality, metastasis, tumor size, the risk of stages, the dose of tyrosine kinase inhibitors, or the rate of complete resection[31]. Our results demonstrated that levels of COX-2 expression were significantly different between gastric tumors and nongastric tumors (P < 0.001), but no significant relationship was found between the COX-2 expression and risk factors, or survival. Imatinib therapy reduces rates of recurrence in GISTs. Nevertheless, it remains unclear how to screen patients who would be more likely to benefit from the adjuvant therapy. In our study, we found that imatinib treatment could significantly improve 3-year DSS rates in the intermediate and high risk categories of patients after a complete tumor resection.

In conclusion, Ki-67 expression is significantly associated with GIST malignancy and can be used as a putative prognostic marker in GISTs. p53 and COX-2 also provide additional valuable information in the evaluation of malignancy and types of GISTs. COMMENTS Background Gastrointestinal stromal tumors (GISTs) are known to have a wide variability in malignancy and prognosis. Risk grading based on tumor size, location and mitotic counts has been proposed to predict adverse outcomes of GIST in the literature. Research frontiers Recent molecular studies have found that the deregulations of Ki-67, cyclin A, B1, D1, E, cdc2 and other cell-cycle regulators were significantly associated with a shorter disease-free survival in GISTs.

Innovations and breakthroughs In this study, expressions of Ki-67, p53, epidermal growth factor receptor (EGFR) and COX-2 were investigated in a large cohort of GIST patients and their roles as prognostic values for GISTs were also evaluated. To our knowledge, this is the first assessment of the prognostic value of EGFR in patients with GISTs. Applications The immunohistochemical staining of these tumorigenetic and cell proliferative proteins provides an alternative approach for follow-up and clinical Carfilzomib decisions regarding the treatment for GISTs.