| BACKGROUND:The thymus epithelial tumors character by a varied histomorphology and frequently associated paraneoplastic autoimmune diseases in which myasthenia is the most common.With consequent varied and disputed classification systems,the 2004 WHO thymic epithelial classification proposed and widespreaded in application for the recent years,which including the thymoma and the thymic cancer.Thymoma then divided into A,AB,B1,B2,B3 and so on.To study the the biology behavior difference of different type has profound clinical value.Objective:Study the significance in application for WHO classification of thymic epithelial tumors by retrospective analysis.Methods:Collected from pathologic department of beijing hospital in February 1990 to April 2008 resection of thymic epithelial tumors of 172 cases which all classified by 2004 WHO standard and staged by images,surgical findings and pathological observation.The integrity clinical and the revisit material of 123 case examples were obtained, follow-up from 12 months to 204 months,and all the patients received neither radiocberapy nor chemocberapy before the surgery.Compared the different pathology type with the sex,the age,the associated myasthenia,Masaoka stages and with the prognosis.Results:In 172 cases,includes 17 cases of thymoma A(9.88%),35-84 years old,average 57.8±13.8 years old,male 8 cases,female 9 cases,of which 8 patients with myasthenia gravis(42.11%),11 patients are followed up for 2-13 years,no cause of death due to tumor;24 cases of type AB thymoma(13.95%),age 21-69 years old, average 48.5±12.2,male 9 cases,female 15 cases,of which 16 cases with myasthenia gravis(64.00%),16 cases of patients followed up for 1-17 years,no cause of death due to tumor;15 cases of B1 thymoma(8.72%),aged 26-75 years old,average age 45.5±15.1 years old,male 7 cases,female 8 cases,of which i0 cases with myasthenia gravis(76.92%),13 patients have follow-up,2-16 year follow-up time, no cause of death due to tumor;53 cases of type B2 thymoma(30.81%), age 19-71 years old,average age 43.9±11.0 years old,male 26 cases,female 27 cases,of which 52 cases with myasthenia gravis (98.11%),40 cases of patients followed up for 1-17 years,2 cases of death due to tumor;44 cases of type B3 thymoma(25.58%),aged 21-75 years old,average age 45.8±13.8 years old,25 cases of male, female 19 cases,of which 39 cases with myasthenia gravis(90.70%), 26 cases of patient follow-up,follow-up period was 1-17 years,four cases of death due to tumor;19 cases of thymic carcinoma(11.05%), aged 31-70 years old,average age 58.2±10.6 years old,10 cases of male,female 9-year-old,of which one cases with myasthenia gravis (5.26%),17 cases of patients followed up for 1-14 years,lO cases of death due to tumor.Conclusion:1.The incidence of B2,B3 thymoma is higher than other types of thymoma.2.Type A thymoma and thymic carcinoma prones to occur in middle-aged and elderly and Other types of thymoma prone to occur in middle-aged and young.3.The incidence of myasthenia gravis in B2,B3 is significantly higher than in other types of thymoma.4.Thymic carcinoma has poor prognosis and high mortality;The prognosis of thymoma is better but B2,B3 thymoma prognosis are worse than the other types. BACKGROUND:Thymic epithelial tumors(Thymic epithelial tumor,TET), including thymic carcinoma and thymoma,are the most common tumors in mediastinum.The thymic carcinoma shows clear histologic and cytologic atypia.Study of the moledular marks expression on thymic epithelial tumors which related to the biological behavior is very important to understand the mechanism of thymic epithelial tumors and the biological behavior then to improve the level of clinical treatment.Objective:To observe the cell cycle regulator proteins P27,P21, P16,neurotrophin receptor p75 and nuclear antigen Ki67 in thymic epithelial tumor expression and its relationship with WHO classification.Then study the relation between the expression and the neoplastic clinical biology behavior,tumor mechanism.Methods:Collected from pathologic department of beijing hospital in February 1990 to April 2008 resection of thymic epithelial tumors of 172 cases which all classified by 2004 WHO standard and staged by images,surgical findings and pathological observation.The integrity clinical and the revisit material of 123 case examples were obtained,follow-up from 12 months to 204 months,and all the patients received neither radiocherapy nor chemocherapy before the surgery.Using immunohistochemistry(SP method)to study p27,p21, p16,p75,Ki67 in thymic epithelial tumors,specially,in the lymphocyte-rich AB and Bl thymomas using double labeling immunohistochemistry sp for Ki67 marker.The immunohistochemical localization of p27,p21,Ki67 was the nucleus positive,of p16 was nucleus and cytoplasmic positive,of p75 was the cell membrane or cytoplasmic positive.When the expression is observe,then count it positive,if not,negative,In ki67 expression,the percentage of positive cells in 1000 tumor cells was recorded(Ki67 LI).p27,p21, p16,p75 expression and their mutual relations are study by X2 test and Fisher exact test with bilateral,the relations among ki67 index,WHO classification and clinical stage are explored using oneway ANOVA test,the difference was significant when P＜0.05,So as to explore differences of the expression in all kinds of WHO classification of thymoma and thymic carcinoma.Results:In p27 staining,type A 17 cases,17 cases were positive (100%);type AB 24 cases,24 cases were positive(100%);type B1 13 cases,13 cases were positive(100%);type B2 53 cases,51 cases were positive(96.23%),type B3 43 cases,42 cases were positive (97.67%);thymic carcinoma 19 cases,16 cases were positive(84.21%).In p27 expression between different thymoma type there was no significant difference,the positive rate in thymoma (98.00%) was higher than in thymic carcinoma(84.21%),there are significant differences(p＜0.05).In p21 staining,type A 17 cases,4 cases were positive(23.53%);type AB 24 cases,3 cases were positive(12.50%);type B1 13 cases,3 cases were positive (23.08%);type B2 53 cases,30 cases were positive(56.60%),type B3 43 cases,20 cases were positive(46.51%);thymic carcinoma 19 cases,13 cases were positive(68.42%).In p21 expression positive rate(52.08%) in B2,B3 thymoma group was higher than in A,AB,B1 group(18.52%),there are significant differences:the positive rate in thymoma(40.00%) was lower than in thymic carcinoma (68.42%),there are significant differences(p＜0.05).In p16 staining,type A 17 cases,17 cases were positive(100.00%);type AB 24 cases,23 cases were positive(95.83%);type B1 13 cases,12 cases were positive(92.31%);type B2 53 cases,47 cases were positive(88.68%),type B3 43 cases,33 cases were positive (76.74%);thymic carcinoma 19 cases,12 cases were positive(63.16%).In pl6 expression positive rate(46.67%) in B2,B3 thymoma group(83.3%) was lowerer than in A,AB,B1 group (96.3%),there are significant differences:the positive rate in thymoma(88.00%) was higher than in thymic carcinoma(63.00%), there are significant differences(p＜0.05).In p75 staining,type A 17 cases,17 cases were positive(100.00%);type AB 24 cases,15 cases were positive(62.50%);type B1 13 cases,10 cases were positive (76.92%);type B2 53 cases,22 cases were positive(41.51%),type B3 43 cases,21 cases were positive(48.84%);thymic carcinoma 19 cases,11 cases were positive(57.89%).In p75 expression positive rate in B2,B3 thymoma group(44.8%) was lowerer than in A,AB,B1 group(77.8%),there are significant differences:the positive rate in thymoma(56.67%) and in thymic carcinoma(57.89%) has no significant differences(p＞0.05).In Ki67 staining,type A 17 cases, Ki67 index 0%—4.69%,average 1.76±0.32%:type AB 24 cases,Ki67 index 0.23%—5.34%,average 2.25±0.33%:type B1 13 cases,Ki67 index 00.04%—12.5%,average 2.56±3.85%;type B2 53 cases,Ki67 index 0.12%—13.17%,average 4.89±0.43%;type B3 43 cases,Ki67 index 1.32%—22.35%,average7.31±0.63%;Thymic carcinoma 19 cases, Ki67 index 4.00%—68.80%,average24.89±3.66%;Ki67 index in thymic carcinoma(24.89%) is higher than thymoma B3(7.31%);in type B3(7.31%) is higher than thymoma B2(4.89%);in type B2(4.89%) is higher than thymoma B1(2.63%);between type A,AB,B1,there is no significant difference in Ki67 index.Conclusion:The expression of CDKIs p27,p21,pl6 are significant different in the thymoma and thymic carcinoma.The expression of CDKIs p21,p16 and p75NTR is significant between group A,AB,B1 and group B2,B3.Suggested that P27,p21,p16 and P75NTR has the role in the occurrence and differentiation in thymoma and thymic carcinoma. It has value in determining thymoma type and differential diagnosis between thymoma and thymic carcinoma.Ki67 index was significantly higher in thymic carcinoma than that in thymoma.Ki67 index in the different subtypes are significant different,Suggesting an important clinical value.
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