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Serosal Penetration Is An Important Prognostic Factor of Gastrointestinal Stromal Tumors: Implication for Classification Systems?
Daniel Vallbohmer*1, Hanke E. Marcus1, Hartmut SchäFer1, Stephan E. Baldus2, Jan Brabender1, Georg Lurje1, Uta Drebber3, Ralf Metzger1, Arnulf H. HöLscher1, Paul M. Schneider4
1Department of Surgery, University of Cologne, Cologne, Germany; 2Institute of Pathology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; 3Institute of Pathology, University of Cologne, Cologne, Germany; 4Department of Visceral and Transplantation Surgery, University Hospital Zurich, Zurich, Switzerland

Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. While some lesions remain stable, others progress rapidly to metastatic disease. Apart from adverse prognostic factors, including peritoneal or distant metastases, prediction of clinical outcome in patients with GISTs remains difficult. There are several histopathologic classification systems that aim to assess the malignant potential of GISTs, with the majority using tumor size and mitotic index as prognostic variables. This study aimed to evaluate the prognostic value of these classification systems in patients with GISTs and characterize other potential prognostic indicators.Patients and
Methods: From 1996 to 2002, 264 patients with mesenchymal tumors were treated in our institution. Of these, 25 (9.5 %) patients had a histopathologic confirmed GIST, all expressing the CD117 antigen (c-KIT receptor tyrosine kinase). Tumor size, mitotic rate, Ki-67 proliferation index and serosal penetration were analyzed to identify patterns that predict clinical outcome. The histopathologic classification systems according to the WHO, Franquemont (modified by using the Ki-67 proliferation index), Fletcher and Miettinen were applied to determine the predictive prognostic implication of the four commonly used classification systems.
Results: A Ki-67 proliferation index ≥ 5%, mitotic rate ≥ 5/50 high power-fields and a histopathologically documented serosal penetration were significantly correlated with a shorter overall survival (p<0.001; p<0.047; p<0.016; log-rank test), whereas a tumor size >5cm had only a tendency towards a worsened prognosis (p=0.07). Survival of patient groups defined by the WHO and modified Franquemont classification system identified significant prognostic differences (p<0.032; p<0.03), while the classification system by Miettinen showed a trend (p=0.059) and by Fletcher no significance (p=0.12).
Conclusion: The Ki-67 proliferation index is a highly significant prognostic factor for patients with GISTs. Therefore, the modified classification system by Franquemont, the only model that combines the three potential prognostic factors, the immunhistochemical parameter Ki-67 proliferation index and the histopathologic factors tumor size and mitotic index, appears to be good prognostic model as well as the WHO classification. Furthermore, our data show for the first time that serosal penetration is another sensitive prognostic indicator for this tumor entity. Our data are hypothesis generating and should be validated in larger clinical studies.


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