Nevertheless, the role of the type of KIT exon 11 mutations for t

Nevertheless, the role of the type of KIT exon 11 mutations for the response and survival under imatinib remains to be determined. Thus, to better understand the prognostic significance of the type of KIT exon 11 deletions, we have compared the clinical characteristics and outcome of Cisplatin clinical trial patients with GIST and deletion of both Tyr568 and Tyr570 with the most frequent deletion of KIT exon 11, delWK557�C558. Materials and methods Patient selection From database of two French pathology departments which detect KIT and PDGFRA mutations in routine practice (Ambroise Pare Hospital, Boulogne; Bergonie Institute, Bordeaux, France), we searched retrospectively for all consecutive patients with GIST and with either delWK or deletions including both residues Tyr568 and Tyr570 (delTyr).

Mutations within exon 9, 11, 13 and 17 of KIT and within exon 12 and 18 of PDGFRA were detected as previously described (Emile et al, 2002, 2004; Heinrich et al, 2003; Hostein et al, 2006). Pathology All samples were obtained before treatment with imatinib. Paraffin-embedded samples were independently analysed by at least two pathologists. For resected GIST, largest tumour diameter and mitotic count per 50 high-power fields (HPF) were evaluated after surgery in each case, as recommended by international criteria and used to evaluate the risk of GIST malignancy (Fletcher et al, 2002; Miettinen and Lasota, 2006). Immunohistochemistry was performed with anti-CD117 (A-4502, polyclonal; DAKO, Copenhagen, Denmark). Clinical data and survival analysis Medical records of all patients were retrospectively reviewed.

Response rates to imatinib were evaluated by spiral computerised tomography according to the RECIST criteria. The relapse-free survival (RFS) was defined as the time between the date of curative surgery and the date of relapse. The progression-free survival (PFS) was defined as the time between the first day of imatinib and the date of progression or death. Overall survival (OS) under imatinib was defined as the time between the first day of imatinib and the date of death or last follow-up. Statistical analysis Results are expressed as medians and ranges. The cut-off date for the final analysis was 15 January 2008. We used Student’s t-test to compare quantitative data in univariate analyses and ��2-tests were used for qualitative data.

We estimated RFS, PFS and OS using the Kaplan�CMeier method, and we used log-rank tests to compare the survival curves (Kaplan and Meier, 1958). SAS software v 9.1 (SAS Institute Inc., Cary, NC, USA) was used for all statistical analysis. Results Mutation, clinical and pathologic characteristics A total of 68 patients with GIST, diagnosed between 1985 and 2007, and all CD117 positive, were retrieved. DelWK and delTyr accounted for 18% (34/185) and 10% (19/185) of KIT exon 11 mutations in Ambroise Cilengitide Par��’s series, respectively.

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