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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endometrial serous carcinoma (ESC) is the most aggressive subtype of endometrial cancer. Its aggressive behavior and poor clinical outcome may be partially attributed to lack of early diagnostic markers and unclear patho-genesis. The transcription factor Erythroid-E2-related factor 2 (Nrf2) is a recently identified protein marker, which plays a role in carcinogenesis as well as responsible for poor prognosis of many human cancers. The aim of this study is to determine the Nrf2 expression in benign endometrium (n=28), endometrial cancers (n=122) as well as their precursor lesions (n=81) trying to see whether Nrf2 has any diagnostic usage and is potentially involved in endometrial carcinogenesis. The level of Nrf2 was evaluated by immunohistochemical (IHC) and verified by using Western blots. Among the malignant cases, Nrf2 was positive in 28 (68%) of 50 ESCs, which was significantly more than in 3 (6%) of 50 endometrioid carcinomas (p < 0.001) and 2 (13%) of 15 clear cell carcinomas (p = 0.001) and other histologic types of endometrial cancers. Among endometrial precursor lesions, both serous endometrial glandular dysplasia (EmGD, 40%) and serous endometrial intraepithelial carcinoma (EIC, 44%) showed a significantly higher Nrf2 expression than that in atypical endometrial hyperplasia or endometrial intraepithelial neoplasia (0%), clear cell EmGD (10%), and clear cell EIC (25%), respectively. We conclude that Nrf2 overexpression is closely associated with endometrial neoplasms with serous differentiation. Alteration of Nrf2 expression may represent one of the early molecular events in ESC carcinogenesis and overexpression of Nrf2 may used as a diagnostic marker in surgical pathology.
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PMID:Nrf2 expression in endometrial serous carcinomas and its precancers. 2122 30

Endometrial cancer is the most frequently occurring malignancy of the female genital tract in Western countries. Although in many cases surgically curable, about 30% of the tumours represent an aggressive and untreatable disease. In an attempt to establish a reliable prognostic marker for endometrial carcinomas disregarding their histological diversity, we investigated the expression of KPNA2, a mediator of nucleocytoplasmic transport, and other cell proliferation-associated proteins and their correlation with cancer progression. We analysed patient tissue microarrays (TMAs) assembled from 527 endometrial cancer tissue specimens and uterus samples from a Trp53 knockout mouse model of endometrial cancer. Our data show that KPNA2 expression was significantly up-regulated in human endometrial carcinomas and associated with higher tumour grade (p = 0.026), higher FIGO stage (p = 0.027), p53 overexpression (p < 0.001), activation of the PI3K/AKT pathway, and epithelial-mesenchymal transition. Increased nuclear KPNA2 immunoreactivity was identified as a novel predictor of overall survival, independent of well-established prognostic factors in Cox regression analyses (hazard ratio 1.7, 95% CI 1.13-2.56, p = 0.01). No significant association between KPNA2 expression and endometrial cancer subtype was detected. In the mouse model, KPNA2 showed increased expression levels from precancerous (EmgD, EIC) to far-advanced invasive lesions. We further investigated the cell proliferation capacity after siRNA-mediated KPNA2 knockdown in the human endometrial cancer cell line MFE-296. KPNA2 silencing led to decreased proliferation of the cancer cells, suggesting interplay of the protein with the cell cycle. Taken together, increased expression of KPNA2 is an independent prognostic marker for poor survival. The mechanism of enhanced nucleocytoplasmic transport by KPNA2 overexpression seems a common event in aggressive cancers since we have shown a significant correlation of KPNA2 expression and tumour aggressiveness in a large variety of other solid tumour entities. Introducing KPNA2 immunohistochemistry in routine diagnostics may allow for the identification of patients who need more aggressive treatment regimens.
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PMID:KPNA2 is overexpressed in human and mouse endometrial cancers and promotes cellular proliferation. 2493 Aug 86

The p53 signature (p53S) has been proposed to be a marker of the earliest phase of development of endometrial serous carcinoma. We examined the presence of p53S in the background endometrium in cases of endometrial carcinoma. From a series of 351 endometrial carcinomas, 225 (64.1 %) lesions, for which slides of the adjacent noncancerous endometrium were available for review, were included. Expression of estrogen receptor (ER)-alpha, Ki-67, and p53 in the adjacent endometrium was studied by immunohistochemistry. The p53S was defined as the presence of morphologically benign endometrial epithelial cells with moderate to strong intensity of p53 immunostaining. Of the 225 noncancerous endometrium samples, 34 consisted of hyperplastic and 191 of non-hyperplastic endometrium. A p53S was found in 22 cases (mean age 64.2 years), 2 in hyperplastic, and 20 in non-hyperplastic background endometrium. All p53S-positive cases also expressed ER-alpha; their median Ki-67 labeling index (LI) was 4.0 % (range 0.0 to 21.0 %). The two cases with hyperplastic p53S-positive background endometrium were in association with a grade 1 endometrioid tumor in a premenopausal woman with Lynch syndrome. Of the 152 cases of endometrioid adenocarcinomas with non-hyperplastic endometrium, 12 (8 %) were p53S positive, none of which associated with EIC. Of the 21 cases of serous carcinoma, five (24 %) were p53S positive, 4 of which (19 %) associated with EIC while in 5 others (24 %) EIC was found without p53S. Of three clear cell adenocarcinomas, none were p53S positive while two contained EIC without p53S. Of 15 carcinosarcomas, 3 (20 %) were p53S positive, all of which with EIC while 6 others (40 %) were associated with EIC but without p53S. Of the 8 non-endometrioid tumors with p53S, 7 (88 %) were associated with EIC. p53S is thought to be associated with precancerous lesions of non-endometrioid tumors, including carcinosarcomas.
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PMID:Significance of p53 expression in background endometrium in endometrial carcinoma. 2578 66