Table 1.

Tumor changes in imatinib-treated patients

Group A: clinical/radiologic responding 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-1Histologic response assessment (cases)Number of nodules analyzedPrimarySecondaryIP/WB
Primary tumor (pre-imatinib)
KITChromosome 4GENE/CEP4Chromosome 4GENE/CEP4
1180011Liver M3a00High (low cellular/low proliferating)1aExon 11Del 550-558Not presentDisomy (1a)0.97Low polysomy0.93
22800 to >40021Abdominal R1a001aExon 11Del 557+K558ENot presentDisomy (1a)0.99Low polysomy0.95
33400 to > 80017Esophagus + liver M1a001aExon 11K558N+Del 559Not presentDisomy (1a)0.96
4540017Abdominal R3a001aWild typeNot presentTrisomy1.02
56400 to > 80039Abdominal R3a002aExon 11Del 579Not presentDisomy (1a)1.04Disomy0.92
6740020Liver M2a001aExon 11K558N+Del 559-577Not presentDisomy0.97
78400 to > 30019Liver M1aNo availability of tumoral cells
8940016Abdominal R + liver M10 (2 a; 8 b)0<10%1bExon 11W557S+K558T+Del 559Not presentDisomy (1b)1.01Disomy1.13
91040016Abdomen R5 (4 a; 1 b)001aExon 11Del 557-558Not presentDisomy (1b)0.98Disomy1.04
101140020Abdominal R + liver M3 (1 a; 2 b)00 + <10%1bExon 11Del 550-558Not presentDisomy (1b)1Disomy1.03
111280022Abdominal R3 (1 a; 2 b)002 (1a,1b)Exon 11Del 552-558Not presentDisomy (1b)1.07Disomy1.12
121340015Abdominal R1b0<10%1bWild typeNot presentTrisomy (1b)1.12Trisomy0.9
131440013Abdominal R + liver M1b001bExon 11Del 558-562Not present
141540014Abdominal R6 (1 a; 1 b; 2 c; 2 d)00Moderate (cellular/low proliferating)3 (2c,1d)Exon 11K558N+Del 559Not present+++P (1c)Low polysomy (1b, 2d)0.94Disomy1.02
151940020Abdominal R6 (1 a;1 b; 2 c;2 d)003 (1c,2d)Exon 11Del 563-572Not presentHigh polysomy (1c,2d)1.89High polysomy2.34
1620400 to > 200 to > 40025Abdominal R + liver M7 (2 a; 2 b; 2 c; 1 d)00 to <10%2 (1c,1d)Exon 11V559DNot presentDisomy (2a, 1c)0.48Disomy0.95
Low polysomy (1d)0.57
172140026Abdominal R3 (1 c;2 d)00 to <10%2 (1c,1d)Exon 11Q556E+Del 557-558Not presentLow polysomy (1c,1d)1.06Low polysomy0.89
182240015Abdominal R + liver M2 (1 c; 1 d)00 to <10%1dWild typeNot presentneneDisomy1.01
192380015Abdominal R4 (2 c; 2 d)00 to <10%3 (2c,1d)Exon 11Del 552-553+E554KNot present++P (1c)Disomy (2c,1d)0.51Disomy0.56
202580012Abdominal R4d00 to <10%4dExon 9Dupl 502-503Not present+++P (1d)Low polysomy (3d)1.03Low polysomy1.05
212640012Primary small intestine + M6d00 to <10%5dExon 11Del 558-562Not presentDisomy (4d)1.02Disomy0.92
22480022Abdominal R2a>10/50 (13)0 + area 10-20%Low (cellular/high proliferating)1aExon 11Del 552-557Not presentDisomy (1a)0.98Disomy0.96
231680031Abdominal R + liver M4 (1 a; 1 b; 1 c; 1 d)>10/50 (50)20-30%2 (1a,1d)Exon 11Del 557-558Not presentNot done**Disomy0.94
24174007Abdominal R3 (1 a; 1 c;1 d)>10/50 (12)20-30%1cExon 11K558N+Del 559Not presentTrisomy (1a, 1c)1.05
251840016Abdominal R5 (1 a; 1 b; 3 d)>10/50 (47)20-30%3dExon 9Dupl 502-503Not present+++P (1d)High polysomy (1a, 2d)1.35Low polysomy0.91
262440035Abdominal R + liver M7 (2 c; 5 d)>10/50 (18)20-30%4dExon 11Del 579Not presentHigh polysomy (3d)1.22
Disomy (1d)0.98
272740038Abdominal R4d>10/50 (26)>30%4dExon 11V559AExon 13 V654ADisomy (1d)1nene
  • 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%.

  • Into brackets, mitosis mean value is reported (from case 23 to 26).

  • ** No material was left for FISH analysis.