Abstract
Background and AimsConsidering the indication of adjuvant therapy, the recurrence risk for primary gastrointestinal stromal tumor (GIST) after surgery needs to be accurately estimated. However, current risk stratification schemes may still have room for improvement. This study seeks to analyze prognostic factors for primary GISTs from 3 aspects, including clinicopathological parameters, immunohistochemical biomarkers, and gene mutational status, and attempts to find novel valuable factors predicting the malignancy potential of GISTs.MethodsRetrospective data from 114 primary GIST patients after R0 resection were collected. Clinicopathological data was obtained from medical records and re-evaluated. Immunohistochemical analysis was performed using the Tissue Microarray method for Ki67, p16, p27, p53, SKP2, CD133, and actin. KIT gene exons 9, 11, 13, and 17 and PDGFRα gene exons 12 and 18 were tested for mutations using PCR.ResultsUnivariate analysis revealed the following factors as poor prognostic indicators for relapse-free survival with a median follow-up of 50 months: male gender, gastrointestinal bleeding, mitotic index >5/50HPFs, tumor size >5 cm, non-gastric site, necrosis, epithelioid or mixed cell type, surrounding tissue invasion, Ki67>5%, p16>20%, p53 index >10, SKP2>10%, and KIT exon 11 deletion. Besides mitotic index, tumor size and site, SKP2 high expression (RR = 2.91, 95% CI: 1.41–5.99, P = 0.004) and KIT exon 11 deletion (RR = 2.73, 95% CI: 1.04–7.16, P = 0.041) were also independent risk factors in multivariate analysis, with gastrointestinal bleeding also showing a trend towards significance (RR = 1.88, 95% CI: 0.98–3.64, P = 0.059). In addition, gastrointestinal bleeding and SKP2 high expression showed a good ability to stratify high-risk patients further.ConclusionOur results show that gastrointestinal bleeding, SKP2 high expression, and KIT exon 11 deletions may be useful indicators of high recurrence risk for primary GIST patients.
Highlights
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract with an annual incidence of 10–15 cases per million [1,2].The gold standard for treatment of localized primary gastrointestinal stromal tumor (GIST) is surgical resection, tumor recurrence or metastasis is common, in the liver and peritoneum [3]
Tumor size, and tumor site, which can be important prognostic predictors for GIST patients, form the basis of a few riskstratification schemes that have been developed for operable GIST, including NIH-Fletcher criteria, AFIP-Miettinen criteria (Table S1), and revised NIH consensus criteria [5,6,7]
Gastrointestinal bleeding existed as a primary symptom in 44 patients
Summary
The gold standard for treatment of localized primary GIST is surgical resection, tumor recurrence or metastasis is common, in the liver and peritoneum [3]. Predicting the recurrence risk and malignancy potential of GISTs more precisely remain valuable issues worth exploring. Within the same risk category, the clinical behavior of GIST still vary, and current risk stratification schemes may still have room for improvement [8]. Considering the indication of adjuvant therapy, the recurrence risk for primary gastrointestinal stromal tumor (GIST) after surgery needs to be accurately estimated. This study seeks to analyze prognostic factors for primary GISTs from 3 aspects, including clinicopathological parameters, immunohistochemical biomarkers, and gene mutational status, and attempts to find novel valuable factors predicting the malignancy potential of GISTs
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