p27 Labeling index and proliferation in gastrointestinal stromal tumors: correlations with clinicopathologic factors and recurrence

BACKGROUND: Low expression of p27, a cyclin-dependent kinase inhibitor, has recently been reported to be associated with poor prognosis of many tumors. Moreover, an inverse relationship between p27 expression and proliferation was also noted. Although accumulating data indicate a correlation between high proliferation rate and aggressive behavior of gastrointestinal stromal tumors, no conclusive correlation between p27 expression and either tumor recurrence or proliferation has been established yet in this disease. The aim of this study was to immunohistochemically investigate the association of p27 expression (as measured by the p27 labeling index: p27LI) with recurrence and proliferation (as measured by the Ki-67 labeling index: KLI) in gastrointestinal stromal tumors. METHODS: p27LI and KLI were investigated in tumor specimens from 50 patients diagnosed with gastrointestinal stromal tumors. Quantitative evaluations of p27LI and KLI were performed on tissue sections stained immunohistochemically with anti-p27 and anti-Ki-67 monoclonal antibodies. RESULTS: Both p27LI and KLI were associated with the presence of recurrence and high mitotic index. A significant inverse correlation was noted between p27LI and KLI (r = -0.82). The recurrence-free survival time was significantly shorter in patients with high KLI (> or = 10%), low p27LI (<18%), mitosis (> or = 4), and larger tumor size (> or = 5.2 cm). Multivariate analysis indicated that p27LI, KLI, and mitosis were independent predictors of recurrence-free survival. CONCLUSIONS: These findings support the view that p27LI is a reliable marker in predicting recurrence and recurrence-free survival in gastrointestinal stromal tumors. Moreover, the concordance of high KLI together with low p27LI, and vice versa, might allow us to measure the aggressiveness of these tumors.