The Expression And Significance Of C-myc,c-fos And Proliferating Cell Nuclear Antigen (PCNA) In Thymomas

Background and Objective: Thymoma, which originates from the thymicepithetlial cells, is one of the most common anterior mediastinal tumors and accounts for 15%-20% of all mediastinal mass.Thymoma should be considered as the potential or early stage of a malignant neoplasm because of its local invasion. Some investigations have been made by scholars, but they didn't make quick progresss since the morphological and functional complexity of thymus.The occurrence and development of tumors are a very complex biological process with multi-factor, multi-gene, and multi-phases and oncogenes play pivotal roles in this process.Scientists have done some research on the role of oncogenes in thymomas, but the genetic background of thymomas remains largely unknown.Oncogene c-myc is one of the most important genes in cell cycle. Its expression alters cell proliferation, cell growth, differentiation, and metabolism. The central role of c-myc in malignant transformation of human and animal cells has been proved. Types of human malignant tumors have been reported to have amplification or overexpression of this gene. Oncogene c-fos belongs to immediate-early gene (IGE). The c-Fos protein heterodimerizing with c-Jun protein make up of the activator protein-1 (AP-1), which is a transcription factor. Overexpression of c-fos is involved in many human malignant tumors. Proliferating cell nuclear antigen(PCNA) is a processivity factor for replicative DNA polymerase 8 . The detection of PCNA with immunohistochemical methods is a common way to study the proliferating activity ofcancer cells. The PCNA expression is a useful marker for evaluating malignant grade, and for predicting recurrence and prognosis of many malignant tumors.In our study, immunohistochemical SP assay was used to detect the expression of c-myc, c-fos and proliferating cell nuclear antigen (PCNA) in the thymomas, and to correlate the expression with the clinical significance and prognosis. And it may provide basis of research to the gene diagnosis and gene therapy.Materials and methods: Forty-one cases of thymoma were treated bythymectomy in the second affiliated hospital of Zhengzhou University from January 2001 to April 2004. All the specimens were 10% formalin-fixed and paraffin-embedded.The 41 thymoma cases, 23 male and 18 female, aged between 18 to 70 years, average age is 42.3 ± 14.9. The HE staining sections were affirmed and histopathologic types were classified by two pathologist.According to the WHO histological classification system, 41 patients had 3 A type, 7 AB type, 15 B1 type, 6 B2 type ,10 B3 type and 0 C type.There were 10 benign(type A/AB) thymomas and 31 malign(type B1~B3) thymomas.The tumors were also staged based on Masaoka system, 12 stage Ⅰ , 15 stage Ⅱ, 11 stage Ⅲ and 3 stage Ⅳ .There were 12 non-invasive(stage Ⅰ ) thymomas and 29 invasive(stage Ⅱ — Ⅳ ) thymomas. 18 non-neoplastic thymus were chose as common comparison.Four 4μm thick sections were prepared, three prepared for immunohistochemical assay,and one for HE staining. We use Immunohistochemical SP assay to detect the expression of c-myc ,c-fos and PCNA in thymomas.The results were analysis by SPSS 10.0 statistical software.The chi-square test were used to process the data, a =0.05 were considered as the significant test level.Results: (1) The positive rates of c-myc in thymomas and non-neoplastic thymus were 63.4%(26/41) and 16.7%(3/18) and the difference was significant (p<0.01). The positive rate of c-myc expression in WHO type A/AB and WHO type B1~B3 were 30.0%(3/10) and 74.2%(23/31),there was significant difference(p<0.05). The positive rate of c-myc expression in Masaoka stage Ⅰ and stage Ⅱ ~ Ⅳ were 33.3%(4/12) and 75.9%(22/29), there was significant difference (p<0.05). (2) Thepositive rate of c-fos in thymoma was 34.1%(14/41),while the positive rate of c-fos in non-neoplastic thymus tissue was 5.6%(1/18). The difference was significant (p<0.05). The positive rate of c-fos expression in WHO type A/AB and WHO type B1~B3 were 30.0%(3/10) and 35.5%(ll/31),there was not significant difference(p>0.05). The positive rate of c-fos expression in Masaoka stage Ⅰ and stage Ⅱ ~ Ⅳ were 25.0%(3/12) and 37.9% (11/29), there was not significant difference(p>0.05). (3) The high expression rate of PCNA in thymoma and non-neoplastic thymus was 65.9% (27/41) and 22.2% (4/18), the difference was significant (p<0.01). The high expression rate of PCNA expression in WHO type A/AB and WHO type B1~B3 were 30.0% (3/10) and 77.4% (24/31),there was significant difference(p<0.05). The high expression rate of PCNA expression in Masaoka stage Ⅰ and Ⅱ ~Ⅳ were 25%(3/12) and 82.8% (24/29), there was significant difference(p<0.01). (4) 27 high expression of PCNA had appeared 21 positive expression of c-myc.The positive expression of c-myc was significant correlated to the expression of PCNA(p<0.01). 27 high expression of PCNA had appeared 11 positive expression of c-fos.The positive expression of c-fos was not correlated to the expression of PCNA(p>0.05).Conclusion: (1) c-myc and PCNA correlate with the proliferating activity ofthymoma. (2) c-myc,c-fos and PCNA play an important role in the occurrence and development of thymoma. (3) The expression of c-myc and PCNA correlates with the malignance of thymoma.Testing the expression of c-myc and PCNA in thymomas will be helpful to predict the aggression and progression. Patients with positive expression of c-myc or high expression of PCNA should be followed up after operation to reduce local recurrences and metastases.