Factors associated with disease progression in patients with gastrointestinal stromal tumors in the pre-imatinib era.

The aim of this study was to determine the predictors of survival in 38 patients with curatively resected gastrointestinal stromal tumors (GISTs). The tumor was located in the stomach in 23 cases, the small bowel in 13, and the colon in 2. In 23 patients (61%), a mutation in exon 11 of the kit gene was detected. In 7 cases, all small gastric tumors, a mutation in the platelet-derived growth factor receptor a (PDGFRA) gene was detected. The overall 5-year survival rate was 70%. In 9 patients, GISTs relapsed, leading to an actuarial 5-year disease-free survival of 78%. By multivariate analysis, the presence of distant metastases, the proliferative (MIB-1) index, and deletional mutation in codons 557 and/or 558 of kit exon 11 correlated significantly with poor outcome. None of the PDGFRA mutant GISTs relapsed. These findings suggest a strong relationship between various tyrosine kinase receptor mutations and survival outcome in patients with GISTs.

[1]  B. Nilsson,et al.  Gastrointestinal stromal tumors: The incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era , 2005, Cancer.

[2]  P. Morel,et al.  Are there any prognostic factors for small intestinal stromal tumors? , 2004, American journal of surgery.

[3]  A. D. Van den Abbeele,et al.  Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  E. Wardelmann,et al.  Deletion of Trp‐557 and Lys‐558 in the juxtamembrane domain of the c‐kit protooncogene is associated with metastatic behavior of gastrointestinal stromal tumors , 2003, International journal of cancer.

[5]  M. Ladanyi,et al.  Association of KIT exon 9 mutations with nongastric primary site and aggressive behavior: KIT mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[6]  D. Brewster,et al.  Prognostic indicators for gastrointestinal stromal tumours: a clinicopathological and immunohistochemical study of 108 resected cases of the stomach , 2003, Histopathology.

[7]  Huichang Yan,et al.  Prognostic Assessment of Gastrointestinal Stromal Tumor , 2003, American journal of clinical oncology.

[8]  Samuel Singer,et al.  PDGFRA Activating Mutations in Gastrointestinal Stromal Tumors , 2003, Science.

[9]  L. Guillou,et al.  Elevated (≥10%) MIB-1 Proliferative Index Correlates with Poor Outcome in Gastric Stromal Tumor Patients: A Study of 35 Cases , 2002, Digestive Diseases and Sciences.

[10]  J. Fletcher,et al.  Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  A. D. Van den Abbeele,et al.  Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. , 2002, The New England journal of medicine.

[12]  L. Sobin,et al.  Diagnosis of gastrointestinal stromal tumors: A consensus approach. , 2002, Human pathology.

[13]  M. Heinrich,et al.  KIT mutations are common in incidental gastrointestinal stromal tumors one centimeter or less in size. , 2002, The American journal of pathology.

[14]  W. El-Rifai,et al.  Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: a review. , 2002, Human pathology.

[15]  C. J. Chen,et al.  KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. , 2001, Cancer research.

[16]  Sigrid Stroobants,et al.  Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study , 2001, The Lancet.

[17]  L. Sobin,et al.  Gastrointestinal Stromal Tumors, Intramural Leiomyomas, and Leiomyosarcomas in the Duodenum: A Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of 167 Cases , 2001, The American journal of surgical pathology.

[18]  M. Debiec‐Rychter,et al.  Chromosomal aberrations in malignant gastrointestinal stromal tumors: correlation with c-KIT gene mutation. , 2001, Cancer genetics and cytogenetics.

[19]  S. Hirota,et al.  Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors. , 1999, Cancer research.

[20]  Edvardsson,et al.  Expression of c‐kit (CD117) and Ki67 provides information about the possible cell of origin and clinical course of gastrointestinal stromal tumours , 1999, Histopathology.

[21]  L. Sobin,et al.  KIT mutation portends poor prognosis in gastrointestinal stromal/smooth muscle tumors. , 1998, Laboratory investigation; a journal of technical methods and pathology.

[22]  R. Parwaresch,et al.  Immunophenotype, proliferation, DNA ploidy, and biological behavior of gastrointestinal stromal tumors: a multivariate clinicopathologic study. , 1998, Human pathology.

[23]  S. Hirota,et al.  Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. , 1998, Science.

[24]  J. Tworek,et al.  Stromal tumors of the jejunum and ileum. , 1997, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[25]  J. Rodríguez-Peralto,et al.  Prognostic significance of DNA ploidy and proliferative index (MIB-1 index) in gastrointestinal stromal tumors. , 1997, Human pathology.

[26]  Frierson Hf,et al.  Proliferating cell nuclear antigen immunoreactivity and prognosis of gastrointestinal stromal tumors. , 1995 .

[27]  R. E. Cunningham,et al.  Predicting Prognosis of Gastrointestinal Smooth Muscle Tumors: Role of Clinical and Histologic Evaluation, Flow Cytometry, and Image Cytometry , 1993, The American journal of surgical pathology.

[28]  H. Appelman,et al.  Solitary solid stromal gastrointestinal tumors in von Recklinghausen's disease with minimal smooth muscle differentiation. , 1984, Human pathology.

[29]  P. Åman,et al.  The complexity of KIT gene mutations and chromosome rearrangements and their clinical correlation in gastrointestinal stromal (pacemaker cell) tumors. , 2002, The American journal of pathology.

[30]  R. DeMatteo,et al.  Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. , 2000, Annals of surgery.

[31]  J. Lasota,et al.  Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas. , 1999, The American journal of pathology.

[32]  H. Höfler,et al.  [Prognostic factors of gastrointestinal stromal tumors of the stomach]. , 1998, Verhandlungen der Deutschen Gesellschaft fur Pathologie.

[33]  J. Goldblum,et al.  Stromal tumors of the duodenum. A histologic and immunohistochemical study of 20 cases. , 1995, The American journal of surgical pathology.

[34]  D. Franquemont Differentiation and risk assessment of gastrointestinal stromal tumors. , 1995, American journal of clinical pathology.