Gastric GISTs: Analysis of c-Kit, PDGFRA and BRAF mutations in relation to prognosis and clinical pathological characteristics of patients - A GIRCG study.

BACKGROUND: Gastric gastrointestinal stromal tumors (GISTs) represent a subgroup of GISTs with a better prognosis than those located in other areas. In this retrospective study we performed a molecular characterization of a large series of patients with gastric GISTs in relation to clinical-pathological characteristics and prognosis. METHODS: DNA was extracted from paraffin-embedded sections from 221 gastric GIST patients submitted to surgery. Exons 9, 11, 13 and 17 of KIT, exons 12 and 18 of PDGFRA and exons 11 and 15 of BRAF were analyzed by direct sequencing. Cox regression analysis adjusted for clinical-pathological factors was performed to evaluate KIT and PDGFRA mutations in relation to the composite endpoint of relapse or death. RESULTS: KIT and PDGFRA mutations were observed in 119 (53.8%) and 56 (25.3%) patients, respectively, whereas 46 (20.8%) patients had wild type (wt) disease. Univariable analyses showed that a high Miettinen risk category and the presence of ulceration and KIT deletions were associated with increased risk of relapse or death (p < 0.001; p = 0.0389 and p = 0.002, respectively). After adjusting for Miettinen risk score, KIT deletions remained an independent prognostic factor (HRadj = 2.65, 95% CI [1.15-6.13], p = 0.023). Moreover, KIT deletions in exon 11 codons 557, 558 or 559 were associated with a higher risk of relapse or death than wt tumors (HRadj = 3.29 95% CI [1.64-6.64], p = 0.001). CONCLUSIONS: KIT deletions in exon 11, especially those involving codons 557, 558 or 559, were correlated with a more aggressive gastric GIST phenotype and increased risk of relapse or death.

Response to induction therapy in oesophageal and cardia carcinoma using Mandard tumour regression grade or size of residual foci.

BACKGROUND: Tumour regression grade (TRG) is used to evaluate responses to induction therapy in cancer of the oesophagus or cardia. This study aimed to determine whether inclusion of node category could improve the prognostic accuracy provided by TRG, and explore the prognostic value of an alternative classification based on size of residual foci and node category. METHODS: Patients with oesophageal or cardia cancer treated with neoadjuvant chemoradiotherapy followed by resection were studied. Treatment-induced response at the primary site was evaluated by TRG and by a method whereby patients were classified as having no residual cancer, minimal residual disease (MRD) or as non-responders. RESULTS: Between 2000 and 2007, 108 patients underwent resection. Disease-related survival decreased with increasing TRG in node-negative (N0) patients (P < 0.001), whereas in node-positive (N+) patients it was poor irrespective of TRG (P = 0.241). For N0 disease, 3-year survival in patients with MRD (58 (95 per cent confidence interval 26 to 80) per cent) was intermediate between that in patients with no residual cancer (85 (70 to 93) per cent) and non-responders (28 (4 to 59) per cent). Worst prognosis was for N+ disease (21 (9 to 36) per cent). CONCLUSION: Node category should be considered when evaluating response to induction therapy in oesophageal or cardia cancer. A new classification based on size of residual foci and node category seems promising.