Tamoxifen-associated malignant endometrial tumors: pathologic features and expression of hormone receptors estrogen-α, estrogen-β and progesterone; a case controlled study

Wilder, James L; Shajahan, Shahin; Khattar, Nada H.; Wilder, Dawn M; Yin, Jianhua; Rushing, Rodney S; Beaven, Rick; Kaetzel, Charlotte S.; Ueland, Frederick R.; Nagell, J.R. van; Kryscio, Richard J.; Lele, Subodh M.

doi:10.1016/j.ygyno.2003.10.040

Cited by 33 publications

(22 citation statements)

References 22 publications

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“…The reported higher frequency of carcinosarcoma was also observed in previous studies [15,19,[23][24][25][26][27]. This is the first large study that shows a higher frequency of serous Data presented concern all patients with uterine corpus cancer after breast cancer in the studies who had surgery for their uterine corpus cancer; total number of deaths among the 36 patients in the pooled dataset who had not undergone surgery was 32, 15 patients died from uterine corpus cancer (8 (44%) in the non-users, 0 among patients with\2 years of tamoxifen use, and 7 (64%) among patients with C2 years of tamoxifen use) adenocarcinoma.…”

Section: Discussionsupporting

confidence: 84%

“…The 3-year uterine corpus cancer-specific survival was significantly worse for long-term tamoxifen users than for nonusers, largely due to the less favorable tumor characteristics associated with tamoxifen use [15]. Since then, the stronger risk increase associated with poor prognosis uterine corpus cancers (mainly carcinosarcomas) after tamoxifen use has been confirmed in several studies [19,[23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

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Prognosis of uterine corpus cancer after tamoxifen treatment for breast cancer

Hoogendoorn

Hollema

Boven

et al. 2007

Breast Cancer Res Treat

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Tamoxifen increases the risk of uterine corpus cancer. Since only few, mostly small, studies have examined prognosis of uterine corpus cancer following tamoxifen, we conducted a large retrospective cohort study to further investigate this. We examined histopathologic and immunohistochemical characteristics of 332 patients with uterine corpus cancer following breast cancer, according to tamoxifen use. Survival was examined in the same patients combined with 309 patients from a previous study with updated follow-up. Histological review of all cancers was performed. Long-term tamoxifen users showed a higher proportion of non-endometrioid tumors than non-users (32.7% vs. 17.4%, P=0.004), especially serous adenocarcinomas and carcinosarcomas. An increased proportion of FIGO stage III and IV tumors was also observed (20.0% vs. 11.3%, P=0.049). Within FIGO stage I, both short-term and long-term tamoxifen users showed a higher proportion of tumors limited to the endometrium than non-users (35.7% vs. 22.9%, P=0.049 and 0.004 respectively). Uterine corpus cancers in long-term tamoxifen users were more often steroid receptor-negative (ERalpha, PRA and PRB, P<0.05) and P53-positive (P=0.015). Three-year uterine corpus cancer-specific survival was worse for long-term tamoxifen users than for non-users (82% vs. 93% P=0.0001). The survival difference remained after adjustment for histopathologic and immunohistochemical characteristics (hazard ratio (HR) for >or=2 years tamoxifen=2.4; 95% CI=1.2-4.6). In conclusion, this large study clearly shows that tamoxifen-associated tumors have less favorable histological features and a worse survival. Our results can be applied when weighing risks and benefits of tamoxifen versus other hormonal agents used in the prevention and treatment of breast cancer.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Prognosis of uterine corpus cancer after tamoxifen treatment for breast cancer

Hoogendoorn

Hollema

Boven

et al. 2007

Breast Cancer Res Treat

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“…Immunostaining for these markers was assessed using the H score, which is a summation of the product of staining intensity (range, 0-3) and proportion of cells (range, 0-1) staining. 7 …”

Section: Methodsmentioning

confidence: 99%

Small Cell Carcinoma of the Renal Pelvis and Ureter: Clinicopathologic and Immunohistochemical Features

Miller

Holmäng

Johansson³

et al. 2011

Archives of Pathology &Amp; Laboratory Medicine

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Context.—Small cell carcinoma (SCC) of the renal pelvis and/or ureter is very rare, with only case reports published in the literature. Objective.—To describe the clinicopathologic and immunohistochemical findings in the largest series to date. Design.—A review of a regional cancer registry identified 10 cases diagnosed as SCC from 930 patients with renal pelvic and/or ureteral cancer from 1971 to 1998. The original slides, demographics, treatment, and clinical outcome were reviewed. Representative sections were immunostained for AE1/AE3, cytokeratin 7, cytokeratin 20, CD56, synaptophysin, chromogranin, and thyroid transcription factor 1. Results.—Of the 10 cases, 5 were pure SCC, 2 were mixed (SCC and urothelial carcinoma), 2 were reclassified as poorly differentiated squamous carcinoma, and 1 was reclassified as urothelial carcinoma. The patients with SCC had an age range of 50 to 80 years (median, 72 years) with a female to male ratio of 2.5∶1. All patients had non–organ confined disease. Five of 7 patients died of disease; 4 of those 5 had been clinically followed (median survival, 23 months) and 1 was diagnosed at autopsy. The SCC cases revealed positive staining of the SCC component as follows: AE1/AE3 (7 of 7), CD56 (7 of 7), synaptophysin (6 of 7), thyroid transcription factor 1 (5 of 7), chromogranin (4 of 7), and cytokeratin 7 (1 of 7). None were positive for cytokeratin 20 (0 of 7). Conclusions.—SCC of the renal pelvis/ureter is seen in a predominately female population in Sweden, is clinically aggressive, and has poor survival when presenting at an advanced stage in patients only treated by surgery. An immunostain panel serves as a useful adjunct in classifying these tumors.

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“…Tamoxifen, which clearly enhances survival and reduces recurrence in hormone-sensitive breast cancer is a widely used therapeutic antiestrogenic agent in endometrial cancer. However, many reports reveal that tamoxifen may worsen the endometrial cancer related to ERb (ESR2) expression and hormone-resistant phenotype (Wilder et al 2004). GnRH is an important molecule of the hypothalamus-pituitary-gonadal axis related to estrogen steroidogenes is in vertebrates.…”

Section: Endometrial Cancermentioning

confidence: 99%

GnRH signaling in intrauterine tissues

Wu¹,

Wang²,

Huang³

et al. 2009

Reproduction

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Type I GnRH (GnRH-I, GNRH1) and type II GnRH (GnRH-II, GNRH2), each encoded by separate genes, have been identified in humans. The tissue distribution and functional regulation of GnRH-I and GnRH-II clearly differ despite their comparable cDNA and genomic structures. These hormones exert their effects by binding to cell surface transmembrane G protein coupled receptors and stimulating the Gq/11 subfamily of G proteins. The hypothalamus and pituitary are the main origin and target sites of GnRH, but numerous studies have demonstrated that extra-hypothalamic GnRH and extra-pituitary GnRH receptors exist in different reproductive tissues such as the ovary, endometrium, placenta, and endometrial cancer cells. In addition to endocrine regulation, GnRH is also known to act in an autocrine and paracrine manner to suppress cell proliferation and activate apoptosis in the endometrium and endometrial cancer cells through several mechanisms. Both GnRH-I and GnRH-II exhibit regulatory roles in tissue remodelling during embryo implantation and placentation, which suggests that these hormones may have important roles in embryo implantation and early pregnancy. The presence of varied GnRH and GnRH receptor systems demonstrate their different roles in distinct tissues using dissimilar mechanisms. These may result in the generation of new GnRH analogues used for several hormone-related diseases.

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Tamoxifen-associated malignant endometrial tumors: pathologic features and expression of hormone receptors estrogen-α, estrogen-β and progesterone; a case controlled study

Cited by 33 publications

References 22 publications

Prognosis of uterine corpus cancer after tamoxifen treatment for breast cancer

Prognosis of uterine corpus cancer after tamoxifen treatment for breast cancer

Small Cell Carcinoma of the Renal Pelvis and Ureter: Clinicopathologic and Immunohistochemical Features

GnRH signaling in intrauterine tissues

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