| Thymoma is a rare mediastinal tumors originating from the epithelial cells of the thymus gland. The relationship between Myasthenia Gravis(MG) and thymoma has been repeatedly suggested and epidemiological studies have shown that 30%~50% of the thymoma patients combined with MG clinically. Compared with the thymomas without MG, unique clinical and pathological characteristics and better prognosis were observed in thymomas with MG. However, such studies in China were uncommon, and with the limited cases, the study depth and persuasion was not enough.Taking advantage of the center of MG with large numbers of such patients and in order to further investigate the relationship between thymoma and MG, 161 thymomas were admitted to our hospital from October 2008 to October 2014, with a pathological diagnosis and computed tomography( CT) findings. Clinical and pathological date from all patients were reviewed retrospectively from electronic or paper medical records. The statistical analyses were performed and statistical histograms or survival curves were drew in computer using SPSS. Clinical and pathologicalcharacteristics and prognosis of thymomas with and without MG were further investigated.Decisions on the treatment of thymic tumor are mainly based on the malignancy. Malignancy generally is determined clinically by the WHO pathological classification and surgical Masaoka stage. However both of them are imperfect. A large number of clinical evidence show that even the benign thymoma classified by WHO type often perform highly invasive and local metastasizing. Masaoka stage is performed according to encapsulated tumor and infiltration of neighboring tissues or organs by surgeons. In consideration of individual subjectivity, Masaoka stage can not be used as the criteria standards of tumor nature. So we still need to find an effective marker for thymoma nature. C-kit is a transmembrane tyrosine kinase receptor protein encoded by the proto-oncogene c-kit that maps to chromosome 4(4q11-12). After binding to the ligand, followed by homodimerization and phosphorylation, C-kit begins an intrinsic signalling cascade that controls crucial mechanisms involved in cell proliferation,apoptosis, adhesion, and differentiation. C-kit is frequently overexpression in several human neoplasms, such as gastrointestinal stromal tumors(GISTs), breast carcinomas, small cell lung carcinomas, ovarian carcinomas. The expression of C-kit appears to be closely associated with malignancy, biological characteristics and prognosis. Clinically, Molecular targeted therapy against C-kit have been successfully applied to treatvarious tumors. However, studies addressing the expression of C-kit in thymic epithelial tumors are scanty. During the period 2012 ~ 2014, 75 thymic tumors, confirmed by pathological examination, were included in this study. The specimens were obtained through surgery pathology, and the expression of C-kit was examined using Immunohistochemical method.Our purpose was to find the specific molecular marker to distinguish the nature of the tumor, and to investigate the relationship between C-kit expression and prognosis.The clinical results showed that thymoma patients, whether combined with MG or not, both gave priority to male ones. Compare with thymoma without MG, patients of thymoma with MG tend to be younger with an average age of 45.2(21~76)years old, while the average age for patients without MG was 48.5(11~80)years old. The tumor diameter of thymomas with MG was much smaller than thymomas without MG, with 74.2% of subjects exhibiting a diameter below 5cm,while 75.8% of subjects in thymoma without MG exhibited a diameter above 5cm. Thymomas with MG were obvious in B2 type(53.1%) and thymomas along were in B3 type(39.4%) based on the WHO type,. Based on Masaoka staging, 78.1% of subjects in thymoma with MG were in stage I and II, whereas 51.1% of subjects in thymoma without MG were in stage III and IV.The overall survival rate for 161 patients was 91.4%, the 3-year survival rate 94.4%, and the 5-year survival rate 80.3%. The overallsurvival rate for thymomas with MG and without MG were 95.9% and74.2% respectively(P=0.001), the 3-year survival rate 98.1% and 81.8%respectively(P=0.002), and the 5-year survival rate 91.8% and 42.9%respectively(P<0.001). The overall survival rate was 100% for patients with stage I disease, 96.6% for patients with stage II disease, 88.9% for patients with stage III disease, and 52.9% for patients with stage IV disease respectively(P<0.001); the 3-year survival rate was 100% for patients with stage I disease, 97.7% for patients with stage II disease, 95.8% for patients with stage III disease, and 68.8% for patients with stage IV disease respectively(P<0.001); and the 5-year survival rate was 100% for patients with stage I disease, 91.3% for patients with stage II disease, 72.7% for patients with stage III disease, and 20% for patients with stage IV disease respectively(P<0.001). The overall survival rate among type A~B1, B2 and B3 were 97.8%, 95.5% and 78.0% respectively(P=0.001),the 3-year survival rate 97.4%, 98.2% and 83.9% respectively(P=0.012), and the5-year survival rate 93.8%, 88.9% and 59.1% respectively(P=0.010).Among 161 thymoma patients, the overall survival rate for patients with complete resection and partial resection or no resection were 96.3% and47.1% respectively(P<0.001), 3-year survival rate 97.2% and 58.8%respectively(P<0.001), 5-year survival rate 92.7% and 25.0% respectively( P<0.001). The overall survival rate for stage II patients with complete resection and postoperative radiotherapy after complete resection were96.0% and 100.0% respectively(P=1.000), the 3-year survival rate 95.0%and 100.0% respectively(P=1.000)and the 5-year survival rate 85.7% and100.0% respectively(P=0.467).The results from immunohistochemical study showed that the positive expression rate for C-kit in thymoma and thymic carcinoma were 16.2%and 85.7% respectively. The positive expression rate for C-kit among WHO type A-B1, B2 and B3 patients were 9.5%, 15.4% and 23.8% respectively,and there was statistically significant differences between thymomas(type A-B3) and thymic carcinomas(type C)(P <0.001), but no difference among type A-B1, B2, B3 patients(P=0.449). The overall survival rate for patients with positive expression for C-kit was 70.6%, whereas 93.1% for patients with negative expression for C-kit(P=0.024).Thus we come to the conclusion that, in the presence of the apparent MG symptoms, thymoma with MG tend to be younger and tumor diameter significantly smaller. Based on Masaoka staging, thymomas with MG are predominantly found in early stage I and II, equivalent to B2 type in the WHO classification. MG is a positive prognostic factor for thymoma patients. Masaoka staging is a positive prognostic factor for thymoma patients, but it does not accurately identify the nature of the tumor. The WHO classification may be associated with prognosis, but it could not be considered as a standard for judging tumor malignancy. C-kit is associated with the occurrence and development of thymic tumor, and is a specificmolecular marker for identifing the tumor malignancy. Thymus tissue with positive expression of C-kit trend to be more malignant, while thymus tissue with negative expression of C-kit towards more benign. But further verification at gene level still needs to be performed. The expression of C-kit is related to the prognosis, and patients with positive expression suffer a worse prognosis. The molecular target therapy using C-kit tyrosine kinase inhibitors would become a new effective treatment for thymic carcinoma. The mainstay of thymoma treatment is to achieve complete surgical resection. Postoperative radiotherapy after complete resection for stage II tumors should be recommended routinely to prevent local recurrence. |
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