Table 2.

Tumor changes in imatinib-treated patients

Group B: clinical/radiologic progressing patients
Cases*Clinical findings
c-KIT mutation posttreatment
Dose of imatinib (mg daily)§Duration on imatinib (mo)Tumor siteNumber of nodules examined and residual cellularityMitosisImmunohistochemistry Mib-1 (%)Histologic response assessment (cases)Number of nodules analyzedPrimarySecondaryIP/WB
Primary tumor (pre-imatinib)
KITChromosome 4GENE/CEP4Chromosome 4GENE/CEP4
282880015Abdominal R + liver M5 (4 a; 0 b; 0 c; 1 d)>10/50 (45)>30Low (cellular/high proliferating)1dExon 11Del 557-558Exon 14T670I+++P (1d)Disomy (1d)1.02nene
292940035Abdominal R + liver M3 (1 a; 0 b; 1 c; 1 d)>10/50 (50)20-303 (1a, 1c, 1d)Exon 11V559GNot present++P (1d)High polysomy (1d)0.48High polysomy0.6
303040026Abdominal R7 (1 a; 3 b; 1 c; 2 d)>10/50 (26)>303 (1b, 2d)Exon 9Dupl 502-503Not present+++P (1d)Disomy (1d)0.93Disomy0.96
3131400 to >8006Abdominal R7 (1 c; 6 d)>10/50 (35)20-303 (1c, 2d)Wild typeExon 17D820N+++P (1d)Disomy (1d)1.01Disomy1.03
323240020Abdominal R2d>10/50 (59)>302dExon 11E554A+Del 555-571Exon 13V654ADisomy (1d)1.08Disomy1.02
333380039Abdominal R3 (2 d; 1 e)>10/50 (33)>303 (2d, 1e)Exon 11W557C+Del 558-560Not presentDisomy (1e)0.94Lowpolysomy0.75
343480010Abdominal R + liver M3d>10/50 (49)>303dExon 11W557GExon 13V654ADisomy (1d)0.98Disomy0.97
3535400 to >80021Liver M2e>10/50 (24)>302eExon 11Del 552-560Exon 13V654ADisomy (1e)0.99nene
  • NOTE: PDGFRA was sequenced in all the cases and found wild type for the exons analyzed.

    Abbreviations: R, recurrence; M, metastasis; del, deletion; dupl, duplication; ne, not evaluable; IP, immunoprecipitation; WB, Western blotting.

  • * The numbers in bold in the Cases column represent the patients for which the primary tumor was recovered. In addition, in bold row, the cases in which pre–post-Imatinib tumors were analyzed; small numbers indicate the corresponding case numbers reported in a previous paper (see ref. 17).

  • The same primary c-KIT mutation was detected in each tumor sample before treatment.

  • Biochemical analysis was done on post-imatinib tumors.

  • § These patients belonged to the group of 946 patients of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group trial randomly allocated imatinib 400 mg either once or twice a day. For details, see ref. (16).

  • a, <10%; b, 10% to 50%; c, 50% to 90%; d, >90%; e, 100%.

  • Into brackets mitosis mean value is reported (from case 28 to 31 and case 33).