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Original Articles
- Uterine Malignant Mixed Müllerian Tumors Following Treatment with Selective Estrogen Receptor Modulators in Patients with Breast Cancer: A Report of 13 Cases and Their Clinicopathologic Characteristics
- Byung-Kwan Jeong, Chang O. Sung, Kyu-Rae Kim
- J Pathol Transl Med. 2019;53(1):31-39. Published online December 18, 2018
- DOI: https://doi.org/10.4132/jptm.2018.11.16
- 5,904 View
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- 1 Web of Science
- 2 Crossref
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Abstract
PDF - Background
Breast cancer treatment with selective estrogen receptor modulators (SERMs) increasesthe incidence of uterine malignant mixed Müllerian tumors (uMMMTs). We examine clinicopathologiccharacteristics and prognosis of SERM-associated uMMMTs (S-uMMMTs) and discusspossible pathogenetic mechanisms.
Methods
Among 28,104 patients with breast cancer, clinicopathologicfeatures and incidence of uMMMT were compared between patients who underwentSERM treatment and those who did not. Of 92 uMMMT cases that occurred during the same period,incidence, dose, and duration of SERM treatment, as well as overall survival rate, were comparedfor patients with breast cancer who underwent SERM treatment and those who did not (S-uMMMTvs NS-uMMMT) and for patients without breast cancer (de novo-uMMMT). Histopathologicalfindings and immunophenotypes for myogenin, desmin, p53, WT-1, estrogen receptor (ER) α, ERβ,progesterone receptor, and GATA-3 were compared between S-uMMMT and de novo-uMMMT.
Results
The incidence of S-uMMMT was significantly higher than that of NS-uMMMT (6.35-fold).All patients with SERM were postmenopausal and received daily 20–40 mg SERM. CumulativeSERM dose ranged from 21.9 to 73.0 g (mean, 46.0) over 39–192 months (mean, 107). Clinicopathologicfeatures, such as International Federation of Gynecology and Obstetrics stage andoverall survival, were not significantly different between patients with S-uMMMT and NS-uMMMTor between patients with S-uMMMT and de novo-uMMMT. All 11 S-uMMMT cases available forimmunostaining exhibited strong overexpression/null expression of p53 protein and significantlyincreased ERβ expression in carcinomatous and sarcomatous components.
Conclusions
SERMtherapy seemingly increases risk of S-uMMMT development; however, clinicopathologic featureswere similar in all uMMMTs from different backgrounds. p53 mutation and increased ERβ expressionmight be involved in the etiology of S-uMMMT. -
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- The Effect of Tamoxifen and Pentosan Polysulfate on the Microvessel Density and Cell Proliferation of Dimethylbenzanthracene-Induced Rat Mammary Carcinoma.
- Chan Heun Park, Zhe Piao, Kwang Gil Lee
- Korean J Pathol. 1996;30(2):94-105.
- 1,637 View
- 12 Download
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Abstract
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- Antiestrogen tamoxifen (TMX) is thought to elicit its therapeutic effect by competing with endogenous estrogens for the estrogen receptor. Several more recent studies asserted that the antitumor effect of TMX is not due solely to the inhibition of estrogen receptor-mediated action, but due partly to its capacity to inhibit angiogenesis and impair neovascularization. Despite extensive research and clinical experience with this drug, its exact mode of action in inducing tumor regression is still not clear. The present study is aimed toward the investigation of the effects of TMX on dimethylbenzanthracene- induced rat mammary carcinomas with respect to the tumor response to the drugs, histological changes, cell proliferative acitivity and angiogenesis inhibition, and if TMX has antiangiogenic action, to compare it with that of pentosan polysulfate (PPS), an already known antiangiogenic substance. Female Sprague-Dawley rats, aged 50 days, were divided into normal control, test control (tumor induction by dimethylbenzanthracene), TMX (TMX administration after tumor induction), and PPS (PPS administration after tumor induction) groups. Tumor response to the drug administration was classified according to changes of tumor volume as follows; complete response (CR), partial response (PR), no response (NR), and progressive disease (PD). The response rate of rat mammary carcinomas to the drug administration was significantly higher (p<0.05) in the TMX and PPS groups as compared with the test control group. There was, however, no statistical significance between the TMX and PPS groups. Necrosis was considerably frequent in tumors of the TMX and PPS groups. Hyaline change of the stroma was strikingly more common and marked in the TMX group and it was associated with atrophy of epithelial cells of the tumor glands. Proliferating cell nuclear antigen (PCNA)- labeling index of the tumors was significantly higher (p<0.05) in the tumors with NR and PD of the TMX group when compared with those with PR of the same group, which suggested a higher cell proliferative activity in these response groups. In the PPS group, however, there was no significant difference in PCNA index according to response. Microvessel density of the tumors was significantly lower (p<0.05) in the PPS group as compared with the test control and TMX groups and it was not related with response. The TMX group, however, did not show any significant difference in microvessel density when compared with the test control group. Microvessel density was significantly higher (p<0.05) in tumors with PD than those with PR in all 3 groups, which suggested a positive relation of increase in tumor size and angiogenesis. Based on these results it is thought that TMX and PPS inhibit growth of chemically-induced rat mammary carcinomas. It seems that the antitumor action of PPS is related with its antiangiogenic capability, but that of TMX does not have a relationship with angiogenenesis inhibition.
- Expression of Cyclin D1, Cyclin E, p21Cip1 and p27Kip1 in Chemically Induced Rat Mammary Tumor Treated with Tamoxifen and Transforming Growth Factor-1.
- Tae Jung Jang, Jae Hum Park, Mee Yon Cho, Ki Kwon Kim, Jung Ran Kim
- Korean J Pathol. 2001;35(2):151-157.
- 1,438 View
- 12 Download
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Abstract
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- BACKGROUND
Tamoxifen (TAM) inhibits the action of estrogen by binding to estrogen receptors, and also has non-estrogen receptor mediated cytostatic activities. Transforming growth factor-1 (TGF-1) inhibits the proliferation of many other cell types, such as epithelial, hematopoietic and endothelial cells.
METHODS
We investigated the effects of tamoxifen on the growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors and the expression of cyclin D1, cyclin E, p21Cip1, and p27Kip1 by performing immunohistochemistry and Western blot analysis, and studied whether TGF-1 injection amplified the effects of TAM. When tumor size reached between 10-15 mm in the largest dimension, the rats were divided into 3 groups: DMBA-control group (n=12), DMBA-TAM group (n=14) and DMBA-TAM plus TGF-1 group (n=5).
RESULTS
The consecutive administration of TAM markedly decreased the tumor development compared with the DMBA-control group. The DMBA-TAM and DMBA-TAM plus TGF-1 groups showed decreased expression of bromodexoyuridine, cyclin D1, cyclin E, and p21Cip1 when compared with those of the DMBA-control group. On the other hand, the labeling index of p27Kip1 was higher in the DMBA-TAM plus TGF-1 group than in the DMBA-control group.
CONCLUSION
TAM suppresses tumor development, which may be associated with down-expression of cyclin D1 and cyclin E, and overexpression of p27Kip1, and addition of TGF-1 does not influence tumor development treated by TAM.
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