| Objective:To study WHO histologic classification system, clinicopathologic characteristics and gene genetics change of thymic epithelial tumors with investigating biological feature of the different classification, and providing basement for clearing up the classification of thymic epithelial tumors. The content include:1) The morphology and immunophenotype of 64 cases of thymic epithelial tumor were reviewed and reclassified according to the new WHO classification system. The clinical data were analyzed. To study the clinicopathologic characteristics of thymic epithelial tumors with evaluating the diagnostic reproducibility and clinical relevance of the 2004 WHO histologic classification system.2) chromosome 1 in thymoma of type B3, other type in prophase study and normal thymus tissue were researched by fluorescence in situ hybridization (interval FISH), in order to study if there was difference between thymoma of type B3 and the other types.3) Studying the abnormal expression of c-Jun, p73, CASP9, N-ras those tumor related genes which located in chromosome 1 and EGFR, in order to research the action and mechanism of chromosome 1 and it's genes in the genesis and development of thymoma, as well offering some theory basement for judging prognoses of different types of thymoma and instituting individualized treatment prescription. Methods:Part one:The morphology and immunophenotype of 64 cases of thymic epithelial tumor were reviewed and reclassified according to the new WHO classification system. The clinical data were analyzed. Part two:1 chromosome change in thymoma of type B3 (11 cases), thymic carcinoma (8 cases), type A (2 cases), type AB (19 cases), type B1 (4 cases), type B2 (14 cases) in prophase study and 11 cases of normal thymus tissue was researched by fluorescence in situ hybridization (interval FISH). Part three:Studying the abnormal expression of c-Jun, p73, CASP9, N-ras those tumor related genes located in chromosome 1 and EGFR in thymoma and normal thymus tissue by immunohistochemistry(Envision diplo-footwork). Results:Part one:1) Of 64 cases,55 were thymomas and 9 were thymic carcinomas. Among 55 thymomas,3(5.4%) were type A,19(34.5%) were type AB,4(7.27%) were type B1,15(27.3%) were type B2,12 (21.8%) were type B3,2(3.6%) were mataplastic thymoma. Among 9 thymic carcinomas, 8 were squamous cell carcinomas and 1 was neuroendocrine carcinoma. The most frequent presentations were cough and chest pain. Some cases were identified accidently by routine physical examination.17 cases (30.9%) of thymoma were associated with myasthenia gravis. On CT scanning,53 cases (94.2%) were located in the anterior mediastinum. All type A, AB, B1 thymomas and most B2 thymomas appeared as a well-defined, homogeneous mass, whereas a few B2, most B3 thymomas and all thymic carcinomas were poorly demarcated and heterogeneous. According to Masaoka staging system,20 cases (41.7%) belonged stageâ… ,15 cases(31.3%)stageâ…¡,11 cases (22.9%) stage III and 2 cases (4.2%) stage IV. The histological subtypes of thymic epithelial tumor were significantly correlated with the clinical stage (x2=32.5, P<0.001). Part two: 19 cases (31.7%) of thymus epithelium tumor showed amplification of chromosome 1. There were no case showed amplification of chromosome 1 in normal thymus tissue.Through Fisher's Exact Test, P<0.05, which indicated that there were statistic difference between normal tissue and thymoma, as well between different histological subtypes. The positive ratio of thymic carcinoma (75%,6/8) and type B3 was higher than other type. All 4 cases type B1 were negative. Through chi-square test of four-fold table, the positive ratio of type B3 was similar to thymic carcinoma (P>0.05), and significantly higher than other type thymoma (P<0.05). There were significant difference of gain of chromosome 1 among different clinical stages(x2=9.007, P=0.023). When using group comparison, The levels in late-(stage III and IV)stage significantly higher than which in early-(stageâ… andâ…¡) stage(x2=8.839, P=0.003). There was no significant difference of gain of chromosome 1 between stageâ… and stageâ…¡(x2=0.101, P=0.751). Part three:1) 22 cases (36.7%) of thymus epithelium tumor showed positive expression of c-Jun.There were no case showed positive of c-Jun in normal thymus tissue.Through Fisher's Exact Test, P<0.05, which indicated that there were statistic difference between normal tissue and thymoma. There were statistic difference between histological subtypes also (P< 0.05). The positive ratio of thymic carcinoma (87.5%,7/8) and type B3 (45.5%,5/11) was higher than other type. All cases of type A, B1 and metaplasia were negative. There were significant difference of c-Jun among different clinical stages, which of stage IV(100%)and stageâ…¢(53.3%) were higher than other stages.2) 12 cases(20.0%) of thymus epithelium tumor showed positive expression of N-ras. There were 3 cases (3/11, 27.3%) showed positive of N-ras in normal thymus tissue. Through Fisher's Exact Test, P >0.05, which indicated that there were no statistic difference between normal tissue and thymoma. There were no statistic difference between histological subtypes also (P>0.05). The positive ratio of type A (50%,1/2) and type B3 (45.5%,5/11) was higher than other type. All cases of type B1 and metaplasia were negative. There were no significant difference of N-ras among different clinical stages (P>0.05).3) 30 cases (50.0%) of thymus epithelium tumor showed positive expression of Caspase9, There were 7 cases (7/11,63.6%) showed positive of Caspase9 in normal thymus tissue.There were no statistic difference between normal tissue and thymoma (P>0.05). There were statistic difference between histological subtypes (P<0.05). All cases of type A and metaplasia were positive. All cases of type B1 were negative. There were no significant difference of Caspase9 among different clinical stages (P>0.05).4) 28 cases (46.6%) of thymus epithelium tumor showed positive expression of p73. There were only 1 case (1/11,9.1%) showed positive of p73 in normal thymus tissue. There were statistic difference between normal tissue and thymoma(P<0.05). There was statistic difference between histological subtypes (P<0.05). Through chi-square test of four-fold table, the positive ratio of type B3 was similar to thymic carcinoma (P>0.05), and significantly higher than other type thymoma (P<0.05). There were no significant difference of p73 among different clinical stages(P>0.05).5) 46 cases (76.7%) of thymus epithelium tumor showed positive expression of EGFR. Which signifcantly higher than that in normal thymus tissue (1/11, 9.1%) (P<0.05). There was statistic difference between histological subtypes (P<0.05). The positive ratio of thymic carcinoma (100%,8/8) and type B3 (90.9%,10/11) was higher than other type. All cases of type A and metaplasia were negative. There were no significant difference of EGFR among different clinical stages (P>0.05). Conclusions: Part one:2004 revision of WHO histological classification system for thymic epithelial tumor showed a high degree of repetitiveness. Its correlation with the radiologic, clinical and prognostic aspects is helpful for establishing an appropriate strategy of treatment for the individual case. Part two:Gain of chromosome 1 in thymic epithelial tumor higher than normal thymus tissue, Gain of chromosome 1 in type B3 higher than other types, that suggested chromosome disbalence closely related to type B3 and thymic carcinoma. Gain of chromosome 1 play an important role in development and biological behaviour of thymus epithelium tomour. Gain of chromosome 1 closely related to prognosis of thymus epithelium tomour. Part three:Abnormal expression of EGFR and Tumour related gene in chromosome 1 such as c-Jun, p73, CASP9 and N-ras correlated with generation and biological behaviour of thymus epithelium tumour. The positive ratio of c-Jun,p73 and EGFR in thymus epithelium tomour was significantly higher than that in normal thymus tissue. The positive ratio of c-Jun, p73 and EGFR in type B3 was similer to thymus carcinoma, higher than that in other types. The positive ratio of CASP9 in type B3 was lower than that in type A thymoma. Molecular biological change in type B3 was similer to thymus carcinoma, different from other types.
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