1995 Fiscal Year Final Research Report Summary
Immunopathologic and molecular pathologic study of thymic epithelial tumors
| Project/Area Number |
06670198
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Human pathology
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| Research Institution | Nagoya City University |
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Principal Investigator |
EIMOTO Tadaaki Nagoya City University, Medical School, Professor, 医学部, 教授 (60140779)
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| Co-Investigator(Kenkyū-buntansha) |
TATEYAMA Hisashi Nagoya City University, Medical School, Lecturer, 医学部, 講師 (80207068)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Thymus / Thymoma / Thymic carcinoma / Immunohistochemistry / p53 / Apoptosis / bc1-2 protein / Fas antigen |
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| Research Abstract |
1. p53 protein expression and p53 gene mutation were examined in 34 thymic epithelial tumors. All the tumors were positive for p53 protein. The noninvasive thymomas were predominantly low expressors ; many of the invasive/metastatic thymomas were moderate expressors ; and the thymic carcinomas were moderate to high expressors. The difference in the positivity between thymic carcinoma and each of noninvasive or invasive/metastatic thymomas was significant. The DNA sequencing study confirmed the presence of p53 gene point mutation in all 10 cases examined, including three low expressors. These results suggests that p53 gene mutation is an early event in thymic tumorigenesis, and the p53 protein-positive cells increase with the progression of the tumor.
2. Fas antigen and bcl-2 protein were immunohistochemically examined in 11 noninvasive thymomas, 8 invasive/metastatic thymomas, and 10 thymic carcinomas. The apoptotic cells were also visualized, using the TUNEL method. The Fas expression
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seemed to be related to the tumor cell types in thymoma and was recognized only in a few cells in thymic carcinoma. The bcl-2 protein was negative in all thymomas regardless of the stages, but was positive in all thymic carcinomas, suggesting the usefulness of this protein expression in differentiation of thymic carcinoma from thymoma. The TUNEL method demonstrated a significantly higher positivity in noninvasive thymomas than other thymic tumors, suggesting an important role of apoptosis in thymoma progression.
3. To define the phenotype and kinetics of spindle cell thymoma, the Fas antigen, various cytokeratins, CD1a antigen, and cell proliferation-related antigens (PCNA,MIB1) were immunohistochemically examined in spindle cell-type and nonspindle cell-type tumors in comparison. The spindle cell thymomas were characterized by a higher expression of Fas antigen, relatively higher content of low molecular weight cytokeratins, much less infiltration of CD1a-posiitve cortical thymocytes, and lower proliferative activity of the tumor cells. These results are compatible with the features of thymic medullary epithelium and the benign biologic behavior of this type thymoma. Less
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