Re-appraisal of prognostic factors in primary gastrointestinal stromal tumour. Refining definitions.

Gastrointestinal stromal tumour (GIST) is the most common type of sarcoma and occurs exclusively in the alimentary tract. For patients at presumed high risk of recurrence after surgical resection 3 years of adjuvant treatment is recommended. However, the specificity of risk criteria is low. With the aim of improving prognostication we investigated established and potential risk factors in a population-based cohort, and additional molecular analyses were performed. Tumour rupture is considered a negative prognostic factor but its definition has been at the discretion of the surgeon and its significance varies across studies. We proposed an exact definition, making a distinction between major and minor defects of tumour integrity. Major defects were strongly and independently associated with recurrence whereas minor defects were not. Positive resection margins and peritoneal tumour penetration are both associated with recurrence in gastrointestinal carcinomas, and their negative significance in these tumours has been transferred to the assessment of GIST. In our studies, excluding patients with tumour rupture, these variables were without prognostic importance. Most GISTs are situated in the stomach, and here, they exhibit specific growth patterns: luminal, exophytic or transmural. We demonstrated that these patterns were related to clinical and molecular risk factors as well as prognosis. Furthermore, mutations (tumour genotype) had a characteristic anatomical distribution in the stomach, adding evidence for a link between molecular and anatomical features and clinical course. Our studies have identified patients at particularly high risk of recurrence of GIST; likewise, they singled out patients at low risk despite their having high-risk features according to established criteria. Adjuvant therapy, follow-up and counselling could thereby be made more specific