Intratumoral heterogeneous expression of p53 correlates with p53 mutation, Ki-67, and cyclin A expression in endometrioid-type endometrial adenocarcinomas.
To further elucidate the significance of p53 mutation in endometrial carcinoma, we investigated it in endometrioid-type endometrial carcinomas showing intratumoral heterogeneous p53 expression. In addition, we also examined the correlation of p53 mutation and cyclin A expression, because we previously reported a topological correlation between the expression of p53 and cyclin A. The p53 mutation in exons 5-8 in 54 cases of endometrial carcinoma showing immunohistochemical expression of p53 was examined using microdissected tissue DNAs. Of the 54 p53-positive endometrial carcinomas, 23 (43%) had p53 mutation with a tendency in histologically higher grade tumors. Ten of the 54 showed a heterogeneous p53 expression, and in 9 of the 10 cases, p53 mutation was present only in p53-positive sites, which were often found in histologically less differentiated areas with elevated Ki-67 in the same tumor. Cyclin A expression was topologically observed in p53-positive areas; however, it was noted in both tumors with (12/23, 52%) and without (18/31, 58%) p53 mutation. These results suggest that p53 mutation is a late event and plays an important role in the acquisition of malignant potentials in endometrioid-type endometrial adenocarcinomas. Unexpectedly, accumulation of the p53 protein itself may be important in cyclin A overexpression.
Feng
Yu-Zhen
YZ
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Shiozawa
Tanri
T
Horiuchi
Akiko
A
Shih
Hsien-Chang
HC
Miyamoto
Tsutomu
T
Kashima
Hiroyasu
H
Suzuki
Akihisa
A
Nikaido
Toshio
T
Konishi
Ikuo
I
D000328:Adult; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019925:Cyclin A / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D016158:Genes, p53; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016415:Sequence Alignment; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D019925:Cyclin A; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53