SUGIMURA H. Hamamatsu Univ.School of Medicine, Dept.of Pathol.Associate Professor, 医学部, 助教授 (00196742)
DOBASHI Y. Osaka Univ.Research Institute for amicrobial Diseases, Oncogene Research, Resear, 微生物病研究所, 研究員 (90231456)
MORI M. Tokyo Univ.Fac.of Med.Dept.of Pathol.Instructor, 医学部, 助手 (90210137)
佐藤 明 東京大学, 医学部, 助手
ODA H. Tokyo Univ.Fac.of Med.Dept.of Pathol.Instructor, 医学部, 助手 (40214142)
SATO A. Tokyo Univ.Fac.of Med.Dept.of Pathol.Instructor
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¥6,400,000 (Direct Cost : ¥6,400,000)
Fiscal Year 1993 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1992 : ¥2,600,000 (Direct Cost : ¥2,600,000)
Fiscal Year 1991 : ¥3,300,000 (Direct Cost : ¥3,300,000)
The Spectrum of phenotypic as well as genotypic variations in human thyroid carcinoma were investigated with respect to histopathological classification. In particular, the entity of "poorly differentiated carcinoma (PDC)" which we have previously proposed was tried to be established from biological viewpoint. In the immunohistochemical analysis, for 110 cases of thyroid carcinoma, we reconfirmed the consensus that thyroglobulin and keratin are more frequently expressed in well differentiated carcinoma(WDC) rather than undifferentiated carcinoma(UDC). To the contrary, PCNA, c-erb-B-2, p53 protein were found out to be more frequently overexpressed in UDC.In addition, PDC revealed the intermediate values in terms of the frequency of protein expression listed above.
In chromosomal analysis which was performed in 8 cases of papillary carcinoma, no specific mutation was identified.
For molecular pathological analysis, point mutation of p53 gene between exon 5 to 8 was investigated in each his
tological type by utilizing SSCP and direct sequencing for the cases which were determined to be positive for p53 protein on immunohistochemistry. In 7 cases of WDC, no mutation was identified either in SSCP or in sequencing. In 6 cases of PDC, 2 cases revealed mutations and both were turned out to be one base substitution. In 6 cases of UDC, 4 cases revealed alteration in SSCP, and sequencing showed one-base substitution in 3 cases and two-base insertion in one case.
In summary, we have got involved the project targetting the phenotypic and genotypic characterization of thyroid carcinoma in line with histopathological classification, in significant number of the cases. There are definite differences between WDC and UDC in phonotype as well as genotype.In that sense, PDC exists as an intermediate entity of those two categories. Here, we demonstrated the distict entity of PDC during the process of dedifferentiation from WDC to UDC which is, clinicopathologically, the widely known phenomenon in human thyroid carcinoma. Less