Abstract
BackgroundPrognostic indicators for gastrointestinal stromal tumors (GISTs) are under investigation. The latest risk classification criteria may still have room for improvement. This study aims to investigate prognostic factors for primary GISTs from three aspects, including clinicopathological parameters, immunohistochemical (IHC) expression of PTEN, and Ki-67 labeling index (LI), and attempts to find valuable predictors for the malignancy potential of primary GISTs.MethodsTumor samples and clinicopathological data from 84 patients with primary GISTs after R0 resection were obtained. Immunohistochemical analysis was performed based on tissue microarray (TMA) to estimate expression of PTEN and Ki-67 in tumor cells.ResultsThe cut-off point of Ki-67 LI was determined as 1%, using a receiver operator characteristic test with a sensitivity of 71.7% and a specificity of 64.5%. Univariate analysis demonstrated the following factors as poor prognostic indicators for relapse-free survival (RFS) against a median follow-up of 40.25 months: gastrointestinal (GI) bleeding (P = 0.009), non-gastric tumor location (P = 0.001), large tumor size (P = 0.022), high mitotic index (P < 0.001), high cellularity (P = 0.012), tumor rupture (P = 0.013), absent or low expression of PTEN (P = 0.036), and Ki-67 LI >1% (P = 0.043). Gastrointestinal bleeding (hazard ratio, 3.85; 95% confidence interval, 1.63 to 9.10; P = 0.002) was a negative independent risk predictor in multivariate analysis, in addition to tumor size (P = 0.023), and mitotic index (P = 0.002). In addition, GI bleeding showed a good ability to predict recurrence potential, when included in our re-modified risk stratification criteria.ConclusionsThis study suggests that GI bleeding is an independent predictor of poor prognosis for RFS in primary GISTs. Expression of PTEN and Ki-67 are correlated with high risk potential and may predict early recurrence in univariate analysis.
Highlights
Prognostic indicators for gastrointestinal stromal tumors (GISTs) are under investigation
Our main findings were as follows: (1) GI bleeding, a common manifestation for primary GISTs, was an independent predictor of worse prognosis for relapse-free survival (RFS); (2) the IHC underexpression of PTEN was associated with worse RFS at univariate analysis; (3) a Ki-67 labeling index (LI) >1% was associated with worse RFS at univariate analysis; (4) GI bleeding could be considered an additional prognostic indicator in the GIST risk classification scheme
Our study shows that a Ki-67 LI level higher than 1% is associated with a higher relapse potential of primary GISTs, on univariate survival analysis but not on multivariate analysis, and that mitotic index remains a stable prognostic indicator, on both univariate and multivariate analysis
Summary
Prognostic indicators for gastrointestinal stromal tumors (GISTs) are under investigation. The latest risk classification criteria may still have room for improvement. This study aims to investigate prognostic factors for primary GISTs from three aspects, including clinicopathological parameters, immunohistochemical (IHC) expression of PTEN, and Ki-67 labeling index (LI), and attempts to find valuable predictors for the malignancy potential of primary GISTs. Gastrointestinal stromal tumors (GISTs) constitute the most common mesenchymal neoplasms of the gastrointestinal (GI) tract, and the incidence has increased significantly over the past three decades [1,2]. The application of imatinib mesylate (IM), a small-molecule tyrosine kinase inhibitor, has dramatically promoted the disease-free survival of GISTs. side effects and resistance to IM pose new challenges in the management of GISTs. an accurate risk classification scheme has become increasingly crucial for selecting patients who are most likely to benefit from adjuvant IM therapy. Even the latest risk stratification system may still have room for improvement
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