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      Impact of age and gender on tumor related prognosis in gastrointestinal stromal tumors (GIST)

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          Abstract

          Background

          Risk classification and prediction of prognosis in GIST is still a matter of debate. Data on the impact of age and gender as potential confounding factors are limited. Therefore we comprehensively investigated age and gender as independent risk factors for GIST.

          Methods

          Two independent patient cohorts (cohort I, n = 87 [<50 years]; cohort II, n = 125 [≥50 years]) were extracted from the multicentre Ulmer GIST registry including a total of 659 GIST patients retrospectively collected in 18 collaborative German oncological centers. Based on demographic and clinicopathological parameters and a median follow-up time of 4.3 years (range 0.56; 21.33) disease-specific-survival (DSS), disease-free-survival (DFS) and overall survival (OS) were calculated.

          Results

          GIST patients older than fifty years showed significantly worse DSS compared to younger patients (p = 0.021; HR = 0.307, 95% CI [0.113; 0.834]). DSS was significantly more favorable in younger female GIST patients compared with elderly females (p = 0.008). Female gender resulted again in better prognosis in younger patients (p = 0.033).

          Conclusions

          Patient age (<50 years) and female gender were significantly associated with a more favourable prognosis in GIST. Extended studies are warranted to confirm our clinical results and to elucidate underlying pathophysiological mechanisms.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12885-015-1054-y) contains supplementary material, which is available to authorized users.

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          Most cited references36

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          Diagnosis of gastrointestinal stromal tumors: A consensus approach.

          D B Longley, Gordon J. Berman, Christopher Fletcher … (2002)
          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.

            Bengt Nilsson, Per Bümming, Jeanne Meis-Kindblom … (2005)
            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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              Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal.

              L Kindblom, H Remotti, F Aldenborg … (1998)
              The interstitial cells of Cajal (ICC) form a complex cell network within the gastrointestinal tract wall where they function as a pacemaker system. Expression of the kit proto-oncogene is essential for the development of this system. The aim of our study was to examine the hypothesis that gastrointestinal stromal tumors differentiate toward cells with an ICC phenotype. Ultrastructurally, 58 stromal tumors were characterized and found to share many features with ICC. Seventy-eight stromal tumors were immunophenotyped, particularly with regard to the kit receptor. All 78 tumors revealed strong, homogeneous immunoreactivity for the kit receptor as did ICC of adjacent and control gastrointestinal walls. Focal hyperplasia and hypertrophy of kit receptor positive cells were also observed in the gastrointestinal wall adjacent to the tumors. CD34 immunoreactivity observed in interstitial cells surrounding Auerbach's ganglia suggests that a subpopulation of ICC is CD34 positive and may explain why 56 of 78 stromal tumors were CD34 positive. Thirty control tumors, including gastrointestinal leiomyomas and leiomyosarcomas, were all negative for the kit receptor. We conclude that gastrointestinal stromal tumors show striking morphological and immunophenotypic similarities with ICC and that they may originate from stem cells that differentiate toward a pacemaker cell phenotype. We propose that the noncommittal name "gastrointestinal stromal tumor" be replaced by gastrointestinal pacemaker cell tumor.
              Article 0 comments Cited 248 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Klaus Kramer: klaus.kramer@uniklinik-ulm.de
                Uwe Knippschild: uwe.knippschild@uniklinik-ulm.de
                Benjamin Mayer: benjamin.mayer@uni-ulm.de
                Kira Bögelspacher: k.boegelspacher@googlemail.com
                Hanno Spatz: hannospatz@hotmail.com
                Doris Henne-Bruns: doris.henne-bruns@uniklinik-ulm.de
                Abbas Agaimy: abbas.agaimy@uk-erlangen.de
                Matthias Schwab: matthias.schwab@ikp-stuttgart.de
                Michael Schmieder: GISTUlm@gmail.com
                Journal
                Journal ID (nlm-ta): BMC Cancer
                Journal ID (iso-abbrev): BMC Cancer
                Title: BMC Cancer
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1471-2407
                Publication date (Electronic): 14 February 2015
                Publication date PMC-release: 14 February 2015
                Publication date Collection: 2015
                Volume: 15
                Electronic Location Identifier: 57
                Affiliations
                [ ]Department of General and Visceral Surgery, University Hospital Ulm, Albert-Einstein-Allee 23, Ulm, 89081 Germany
                [ ]Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, 89075 Germany
                [ ]Department of General and Visceral Surgery, Krankenhaus der Barmherzigen Brüder, Romanstraße 93, München, 80639 Germany
                [ ]Department of Clinical, Institute of Pathology, University of Erlangen, Erlangen, 91054 Germany
                [ ]Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, 70376 Germany
                [ ]Department of Clinical Pharmacology, University Hospital, Tübingen, 72076 Germany
                [ ]Department of Internal Medicine, Alb-Fils-Kliniken, Goeppingen, Goeppingen, 73035 Germany
                [ ]Department of Anesthesiology, Alb-Fils-Kliniken, Goeppingen, Goeppingen, 73035 Germany
                Article
                Publisher ID: 1054
                DOI: 10.1186/s12885-015-1054-y
                PMC ID: 4384379
                PubMed ID: 25886494
                SO-VID: ea80af46-62d3-484d-a5a7-a7c92b49f17b
                Copyright © © Kramer et al.; licensee BioMed Central. 2015
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 25 August 2014
                Date accepted : 29 January 2015
                Categories
                Subject: Research Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2015

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: gist,gastrointestinal stromal tumor,prognosis,outcome,age,gender,sex
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: gist, gastrointestinal stromal tumor, prognosis, outcome, age, gender, sex

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