Relationship between p53 pathway and estrogen receptor status in endometrioid-type endometrial cancer.
We analyzed the mechanism of estrogen receptor (ER) loss and status of the p53 pathway in 64 cases of endometrial cancer. 26.6% (17 of 64) of endometrial cancers lost ER. Methylation of the ER CpG island was significantly related to ER status (P = 0.0074). However, the methylation site of the ER CpG island differed between breast and endometrial cancers. The abnormal expression rate of p14ARF, MDM2, p53, and the p53 pathway were 7.8% (5 of 64), 32.8% (21 of 64), 25.0% (16 of 64) and 53.1% (34 of 64), respectively. There was no significant difference in the overexpression of MDM2 between p53-positive cases (43.8%: 7 of 16) and p53-negative cases (29.2%; 14 of 48) (P = 0.3595). Abnormal p53 was higher in grade 3 tumors (55.6%; 5 of 9) than in grade 1 and 2 tumors (20.0%; 11 of 55) (P = 0.0364). The abnormality of the p53 pathway was higher in grade 3 tumors (88.9%; 8 of 9) than in grade 1 and 2 tumors (47.3%; 26 of 55) (P = 0.0294). However, there was no significant difference in abnormal p53 pathway between ER-negative and ER-positive cases. In endometrial cancer, ER CpG island methylation was the important mechanism of ER loss. However, there was no significant relationship between the p53 pathway and ER status.
Maeda
Kyoko
K
Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, Japan.
Tsuda
Hiroshi
H
Hashiguchi
Yasunori
Y
Yamamoto
Kumio
K
Inoue
Takeshi
T
Ishiko
Osamu
O
Ogita
Sachio
S
D018269:Carcinoma, Endometrioid / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis; D016889:Endometrial Neoplasms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D011960:Receptors, Estrogen / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D004273:DNA, Neoplasm; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011960:Receptors, Estrogen; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2