Clinical Analysis Of Desmoid Tumors And Evaluation Of Its Expression Of KIT And PDGFR Protein

Background Desmoid tumor,also known as aggressive fibromatosis,are rare fibroblastic tumors which derived from deep fascia plane or muscuofascia structures and exhibit a wide range of locally aggressiveness.Their natural history appears to be that of slow,locally invasive growth,although some tumors stop growing and other regress. Function-sparing surgical resection achieving negative margins should always remain the goal,however,questions like the prognostic factors,the presence of gross or microscopic residual disease,the effect of radiation and the optimal treatment are still controversial and remain unanswered.Imatinb has recently been applied to the treatment of recurrent and refractory desmoid tumors in the salvage settings with confirmed response,however,its exact mechanism is still unknown.Purpose To analysis clinical characteristics,prognostic factors and the importance of residual desease of desmoid tumors and evaluate the immunohistochemical expression of C-Kit,PDGFRα,β.Part OnePatients and methods Between January 1987 and December 2007,198 patients treated with surgery at a single institution were retrospectively reviewed,in which 171 patients with extra-abdominal diseases were further analyzed for local relapse rate,excluding those with intra-abdominal diseases,biopsy and metachronous multiple diseases.One hundred and twenty one patients presented with primary disease,whereas 50 patients had a recurrent tumor.Median follow-up was 95 months(4-256 months).Results During the follow-up time,37 patients(19.2%) had a disease progression in the entire group.No patients died of disease.In the resection group,34 patients(18.5%) had a disease progression,in which 28 patients had a local progression,6 patients had a multifocal recurrence,also known as metachronous disease.In the biopsy group,3 patients (33.3%) had a disease progression.In the study group,28 patients had a local progression.Among them,patients with abdominal disease had a local progression rate of 9%(7/78),while patients with extra-abdominal disease had a local progression rate of 22.6%(21/93).The 5-year and 10-year recurrence-free survival rate(PFS) was 83.3%and 82.2%,respectively.Admitted status,tumor size,location,number,margin status and operation type were significant for predicting local progression in univariate analysis.Tumor number was an independent prognostic factor in the multivariate analysis.In the subgroup analysis,tumor size, location,operation type and marginal status were significant prognostic factor in patients with primary disease.However,for recurrent disease,only tumor number was significant for predicting local progression.Adjuvant radiation can increase local progression survival significantly for patients with gross disease residual.Patients with positive resection margin and recurrent disease can benefit from radiation,though not significant statistically.Part TwoPatients and methods Selected 27 paraffin-embedded desmoid tumor samples were stained with the monoclonal antibodies C-kit,PDGFRαand PDGFRβusing Envision method.Clinical characteristics of those patients were retrospectively reviewed for its correlation with the expression of C-kit,PDGFRαand PDGFRβ.Results(1) All the samples were C-kit negative,in which three were background staining positively.(2) PDGFRαexpression were detected in the cytoplasma of elonged desmoid tumor ceils of 14 patients(51.8%),among which Eleven had weak positive expression and three had strong positive expression.(3) PDGFRβexpression can be found both in the membrane and the cytoplasma of tumor cells of 10 patients(29.6%),in which 5 patients had strong positive expression and 5 had weak positive expression.(4) The expression level of PDGFRαprotein were related with age and tumor size(P＜0.05), however,no correlation was found between clincal parameter with the expression of PDGFRβ.Conclusions:(1) For primary disease,it is suggested to be performed with wide excision to obtain microscopically negative margin for tumors located in abdominal or thoracic wall. If it is not feasible in patients with tumors in extremites or head and neck,marginal resection should be at least obtained without tumor exposure or residual.(2) Patients with desmoid tumors can live for a long time with tumors and rarely experience metastasis. Fuction sparing resection with microscopically positive margin or gross residuel disease, followed by adjuvant radiation,can also be a expediency if it is not feasible for a wide excision or negative margin.(3) It is not suggested to wait and see for patients with microscopically positive margins.Complementary wide resection should be considered firstly for these patients.If it is not feasible,adjuvant radiation should be given for a substitute.(4) Adjuvant radiotherapy is suggested to diminish local recurrence in paitents with gross residuel disease,microscopically positive margin and recurrent disease. However,its benefitial for primary disease is still not clear.(5) Patients with multifocal disease had a high recurrence rate than those with single lesion.It is improtant to detect its multicentric propensity in the first treatment.(6) Desmoids are C-kit negative tumors,with possible expression of PDGFRαand PDGFRβprotein.The expression level of PDGFRαwas higher in patients older than 30-yrs and tumors larger than 5cm.(7) Mutational analysis of PDGFR should be further detected,and the exact mechanism of imatinib effeciency still needs further investigation.