Random nuclear p53 overexpression pattern in tamoxifen-mediated endometrial carcinoma.
In a previous paper, we suggested that tamoxifen (TAM)-mediated endometrial carcinogenesis may not involve estrogenic pathways because of random estrogen receptor positivity among endometrial carcinomas with and without TAM treatment for breast cancer. DNA adduct formation (reported in rat liver and human endometrium) was considered to be a more plausible mechanism for TAM-mediated carcinogenesis. To examine the reported correlation between DNA adduct formation and p53, the present study examined p53 expression in the endometrial carcinomas reported in the previous study. Seven endometrial adenocarcinomas associated with long-term TAM treatment for breast carcinoma and 4 carcinomas without TAM treatment but with history of breast carcinoma were immunohistochemically investigated for nuclear p53 expression. The bcl-2 product was also examined. Diffuse and intense nuclear reactivity for p53 protein was present in only one TAM-related case. Essentially, no differences were observed in the bcl-2 staining patterns of TAM-treated and -untreated patients with cancer. Thus, p53 overexpression in endometrial carcinomas occurring in patients with breast cancer seems to be not specific for TAM-treated patients, and, if DNA adduct formation has any role in this type of endometrial carcinogenesis, it may not be related preferentially to p53 gene alteration. Further studies are needed to understand the precise mechanism(s) of the endometrial carcinogenesis.
Kuwashima
Y
Y
Department of Pathology, Saitama Cancer Center, Japan.
Kurosumi
M
M
Kobayashi
Y
Y
Tanuma
J
J
Suemasu
K
K
Higashi
Y
Y
Kasamatsu
T
T
Shiromizu
K
K
Kishi
K
K
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy; D002467:Cell Nucleus / Q000737:chemistry*; D018736:DNA Adducts / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000139:chemically induced* / Q000737:chemistry / Q000648:ultrastructure; D004965:Estrogen Antagonists / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013629:Tamoxifen / Q000009:adverse effects*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D018736:DNA Adducts; D004965:Estrogen Antagonists; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D013629:Tamoxifen