| PurposeTo evaluate the dignosis and differential dignosis value of C-kit protein in GIST. To detect the mutation of C-kit gene in GIST and examine whether the presence of mutation of C-kit gene is important as a prognostic factor.Methods171 GIMT were collected and divided into GIST, leiomyomas and schwannomas. C-kit gene expression and mutation in GIST had been detected by immunohistochemistry and PCR-SSCP. Fisher's exact test, χ2 test and Kaplan-Meier method for postoperative survival with log rank test were used for statistical comparisons. Results1,C-kit gene expression: The rate of C-kit protein expression was 97%(118/122), most of the positive signals were seen in the cytoplasma and cell membrane. The positive rate of C-Kit was no significant difference between different histological grade(χ2=1.167 P>0.05),age(χ2=0 P>0.05),sex(χ2=0 P>0.05),location of tumors(χ2=0.6409 P>0.05),and immunohistochemical phenotypic(χ2=1.0226 P>0.05),histological type(χ2=0 P>0.05). Leiomyomas and schwannomas were typically C-kit and CD34 negative. 2,C-kit gene mutation: C-kit gene mutation was detected in 41.5%(34/82) of GIST. In benign GIST, C-kit gene mutation was not detected; in magligant GIST, the rate of C-kit gene mutation was 54.8%(34/62). Sequence analysis confirmed the presence of two point mutation of Val567-Asp and Ile570-Met in one GIST. 34 mutational cases showed abnormal mobility shifts. Leiomyomas and schwannomas were free C-kit mutation.3,Effect of C-kit mutation on prognosis of GIST: C-kit mutation was associated withdecreased survival(χ2=11.6464, P<0.05).3-year survival of patients was 59%(20/34), which was lower compared with 90%(43/48)survival for patients whose tumors did not bear the mutation of C-kit.Multivariable analysis with COX's proportional hazard model and forward stepwise method indicated that C-kit gene mutation(χ2=8.871, P<0.05), the size of tumor (χ2=5.693, P<0.05),mitotic cell number(χ2=4.958, P<0.05), PCNA index(χ2=7.244, P<0.05), presence of necrosis(χ2=6.250, P<0.05), microscopic invasion to adjacent tissues(χ2=5.595, P<0.05), recurrence(χ2=17.200, P<0.05) and distant metastasis(χ2 =11.283, P<0.05). The presence of C-kit mutation correlated with tumor size(χ2=16.7950, P<0.05), PCNA index(χ2=17.0990, P<0.05), mitotic cell number(χ2=11.2327, P<0.05), presence of necrosis(χ2=4.4036, P<0.05), microscopic invasion to adjacent tissues (χ2 =22.3912, P<0.05), recurrence (χ2=16.333,P<0.05)and distant metastasis(χ2= 12.9649,P<0.05).The age (χ2 =0.0002, P>0.05), sex(χ2=0.1413, P>0.05), location of tumor(χ2=07.5243, P>0.05), cell type(χ2=0.8272, P>0.05), the presence of hemorrhage (χ2 =0.6331, P>0.05) and C-kit expression(χ2=0, P>0.05) were independently related to the presence of C-kit mutation.Conclusions1,C-kit gene mutation and expression may be new useful phenotypic and genotypic markers to distinguish GIST from leiomyomas and schwannoma.2,The C-kit mutation occur preferentially in malignant GIST and might be a clinically useful marker in the evaluation of GIST.3,C-kit mutation is an independent prognostic factor for survival, the C-kit gene should be examined for mutation in exon11 to predict the prognosis of patients with GIST.4,Whereas C-kit mutation is an important factor in the malignant behavior of GIST, it is not the sole molecular alteration associated with maliganancy.
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