Genotype and risk of tumour rupture in gastrointestinal stromal tumour

Br J Surg. 2018 Jan;105(2):e169-e175. doi: 10.1002/bjs.10743.

Abstract

Background: Tumour rupture is a strong predictor of poor outcome in gastrointestinal stromal tumours (GISTs) of the stomach and small intestine. The objective was to determine whether tumour genotype was associated with risk of rupture.

Methods: Rupture was classified according to the definition proposed by the Oslo Sarcoma Group. Since January 2000, data were registered retrospectively for all patients at Oslo University Hospital undergoing surgery for localized GIST of the stomach or small intestine. Tumour genotype was analysed by Sanger sequencing.

Results: Two hundred and nine patients with mutation data available were identified. Tumour rupture occurred in 37 patients. Among the 155 patients with KIT exon 11 mutations, an increased risk of rupture was observed with a deletion or insertion-deletion (25 of 86, 29 per cent) compared with substitutions (5 of 50, 10 per cent) or duplications/insertions (2 of 19, 11 per cent) (P = 0·014). Notably, rupture occurred in 17 of 46 tumours (37 per cent) with deletions involving codons 557 and 558 (del557/558) versus 15 of 109 (13·8 per cent) with other exon 11 mutations (P = 0·002). This association was confined to gastric tumours: 12 of 34 (35 per cent) with del557/558 ruptured versus six of 77 (8 per cent) with other exon 11 mutations (P = 0·001). In multivariable logistic regression analysis, del557/558 and tumour size were associated with an increased likelihood of tumour rupture, but mitotic count was not.

Conclusion: Gastric GISTs with KIT exon 11 deletions involving codons 557 and 558 are at increased risk of tumour rupture. This high-risk feature can be identified in the diagnostic evaluation and should be included in the assessment when neoadjuvant imatinib treatment is considered.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • DNA Mutational Analysis / methods
  • Female
  • Gastrointestinal Neoplasms / complications
  • Gastrointestinal Neoplasms / genetics*
  • Gastrointestinal Neoplasms / pathology
  • Gastrointestinal Stromal Tumors / complications
  • Gastrointestinal Stromal Tumors / genetics*
  • Gastrointestinal Stromal Tumors / pathology
  • Genetic Predisposition to Disease
  • Genotype
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neoadjuvant Therapy
  • Norway
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Rupture / etiology
  • Rupture / genetics
  • Rupture, Spontaneous / etiology
  • Rupture, Spontaneous / genetics
  • Young Adult