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      Incidence and clinicopathologic features of gastrointestinal stromal tumors. A population-based study

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          Abstract

          Background

          Although the diagnostic criteria and pathogenesis of gastrointestinal stromal tumors (GIST) have recently been elucidated, knowledge of the epidemiology of this malignancy is still limited. This study examined the incidence of GIST in the province of Modena, including pathologic features and clinical outcome.

          Methods

          Gastrointestinal mesenchymal tumors identified by the Modena Cancer Registry between 1991 and 2004 were analyzed with an immunohistochemical panel that included staining for CD-117 and PDGFRα. Size, mitotic rate, and other pathologic parameters were recorded. Each tumor was categorized into National Institutes of Health risk categories (very low, low, intermediate, and high risk).

          Results

          One hundred twenty-four cases were classified as GIST. The age-adjusted incidence rate was 6.6 per million. Seventy-five percent of patients were symptomatic; 34% had a previous or concomitant history of cancer. High-risk features were present in 47% of cases. Seventy-eight percent were submitted to radical surgery. After complete resection, the 5-year disease-free survival rates were 94%, 92%, 100%, and 40% for patients at very low, low, intermediate, and high risk, respectively. In multivariate analysis, high risk was the main predictor of recurrence.

          Conclusion

          This population-based study shows that the incidence of GIST in Northern Italy is comparable to that reported in other European countries. Survival was favorable in lower risk categories and in most of the resected cases. In our study, resected patients at very low, low, and intermediate risk had a similar outcome. Our data support the need to consider high-risk patients after complete surgical resection for treatment with the best available approach.

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          Most cited references19

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          PDGFRA activating mutations in gastrointestinal stromal tumors.

          Most gastrointestinal stromal tumors (GISTs) have activating mutations in the KIT receptor tyrosine kinase, and most patients with GISTs respond well to Gleevec, which inhibits KIT kinase activity. Here we show that approximately 35% (14 of 40) of GISTs lacking KIT mutations have intragenic activation mutations in the related receptor tyrosine kinase, platelet-derived growth factor receptor alpha (PDGFRA). Tumors expressing KIT or PDGFRA oncoproteins were indistinguishable with respect to activation of downstream signaling intermediates and cytogenetic changes associated with tumor progression. Thus, KIT and PDGFRA mutations appear to be alternative and mutually exclusive oncogenic mechanisms in GISTs.
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            Diagnosis of gastrointestinal stromal tumors: A consensus approach.

            As a result of major recent advances in understanding the biology of gastrointestinal stromal tumors (GISTs), specifically recognition of the central role of activating KIT mutations and associated KIT protein expression in these lesions, and the development of novel and effective therapy for GISTs using the receptor tyrosine kinase inhibitor STI-571, these tumors have become the focus of considerable attention by pathologists, clinicians, and patients. Stromal/mesenchymal tumors of the gastrointestinal tract have long been a source of confusion and controversy with regard to classification, line(s) of differentiation, and prognostication. Characterization of the KIT pathway and its phenotypic implications has helped to resolve some but not all of these issues. Given the now critical role of accurate and reproducible pathologic diagnosis in ensuring appropriate treatment for patients with GIST, the National Institutes of Health convened a GIST workshop in April 2001 with the goal of developing a consensus approach to diagnosis and morphologic prognostication. Key elements of the consensus, as described herein, are the defining role of KIT immunopositivity in diagnosis and a proposed scheme for estimating metastatic risk in these lesions, based on tumor size and mitotic count, recognizing that it is probably unwise to use the definitive term "benign" for any GIST, at least at the present time. Copyright 2002, Elsevier Science (USA). All rights reserved.
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              Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era--a population-based study in western Sweden.

              Recent breakthroughs regarding gastrointestinal stromal tumors (GIST) and their pathogenesis have redefined diagnostic criteria and have led to the development of molecularly targeted drug therapy. New treatment options mandate more accurate information regarding the incidence, prevalence, clinical behavior, and prognostic factors of GIST. All patients (n=1460) who potentially had GIST diagnosed from 1983 to 2000 in western Sweden (population, 1.3-1.6 million) were reviewed, and 288 patients with primary GIST were identified. The incidence and prevalence of GIST were determined, and predictive prognostic factors, including current risk-group stratifications, were analyzed statistically. Ninety percent of GISTs were detected clinically due to symptoms (69%) or were incidental findings at surgery (21%); the remaining 10% of GISTs were found at autopsy. Forty-four percent of symptomatic, clinically detected GISTs were categorized as high risk (29%) or overtly malignant (15%), with tumor-related deaths occurring in 63% of patients and 83% of patients, respectively (estimated median survival, of 40 months and 16 months, respectively). Tumor-related deaths occurred in only 2 of 170 of patients (1.2%) with very-low-risk, low-risk, or intermediate-risk tumors. The annual incidence of GIST was 14.5 per million. The prevalence of all GIST risk groups was 129 per million (31 per million for the high-risk group and the overtly malignant group). GIST has been under recognized: Its incidence, prevalence, and clinical aggressiveness also have been underestimated. Currently existing risk-group stratification systems based on tumor size and mitotic rate delineate GIST patients who have a poor prognosis. Prognostication in patients with GIST can be refined using a proposed risk score based solely on tumor size and proliferative index. Copyright (c) 2005 American Cancer Society.
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                Author and article information

                Journal
                BMC Cancer
                BMC Cancer
                BioMed Central
                1471-2407
                2007
                20 December 2007
                : 7
                : 230
                Affiliations
                [1 ]Department of Oncology and Haematology, University of Modena and Reggio Emilia, Modena, Italy
                [2 ]Section of Pathologic Anatomy, University of Modena and Reggio Emilia, Modena, Italy
                Article
                1471-2407-7-230
                10.1186/1471-2407-7-230
                2241631
                18096058
                80868f5a-c2a1-4ca9-8d8e-34c165213c6f
                Copyright © 2007 Mucciarini et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 April 2007
                : 20 December 2007
                Categories
                Research Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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