Expression of the cell-cycle regulatory proteins (pRb, cyclin D1, p16INK4A and cdk4) in human endometrial cancer: correlation with clinicopathological features

Semczuk, Andrzej; Miturski, R; Skomra, Danuta; Jakowicki, J

doi:10.1007/s00404-002-0449-6

Cited by 22 publications

(14 citation statements)

References 38 publications

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“…Cyclin D1 protein is not expressed in the normal endometrium or is present only in rare cells. In contrast, immunoreactivity for cyclin D1 has been recorded in 40-69% of endometrial adenocarcinomas, [24][25][26][27][28][29] and in some studies, such an overexpression has correlated with a higher grade or stage. 24,28 Our findings are comparable as most tumors were at least focally positive and eight cases (36%) showed …”

Section: Discussionmentioning

confidence: 99%

Expression of cell cycle regulatory proteins in endometrial adenocarcinoma: variations in conventional tumor areas and in microcystic, elongated and fragmented glands

et al. 2009

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Endometrial adenocarcinomas may show a distinctive pattern of invasion characterized by the presence of microcystic, elongated and fragmented glands, often most evident along the advancing tumor margin. Earlier, we have shown that these changes appear restricted to low-grade endometrioid carcinomas, many of which show focal mucinous differentiation and lymphovascular space invasion. However, the molecular alterations associated with this morphological alteration are not known. In this study, we have examined immunoreactivity for the cell cycle regulatory proteins cyclin D1, p16 and b-catenin in 22 endometrial carcinomas, specifically comparing the results in conventional tumor areas and in foci in which the glands exhibited microcystic, elongated and fragmented appearances. The conventional neoplastic glands exhibited cyclin D1 and p16 expression in most cases, with 450% tumor cells positive in 8 cases and 11 tumors, respectively. Membranous expression of b-catenin was usually preserved, with variable cytoplasmic and nuclear staining. Cyclin D1 and b-catenin predominantly stained cells at the peripheral or basal aspect of the conventional glands, whereas p16 was more uniformly expressed centrally. Tumor foci composed of microcystic, fragmented and elongated glands showed strong expression of cyclin D1 and p16, sometimes in contrast to unstained contiguous or adjacent conventional neoplastic elements, and there was also loss or fragmentation of membranous b-catenin staining. Intravascular tumor cells also expressed cyclin D1 and p16 and therefore the immunostains often highlighted subtle foci of lymphovascular invasion. The heterogenous expression of cell cycle regulatory proteins within endometrial adenocarcinoma illustrates the importance of assessing microanatomical variations in immunoreactivity, particularly at the advancing margin of tumors. The upregulation of cyclin D1 and p16, together with loss of membranous b-catenin expression in microcystic, fragmented and elongated glands, is similar to epithelial-mesenchymal transitions observed in other malignancies and suggests that this pattern of invasion represents an active rather than a degenerative cellular process. Modern Pathology (2009) 22, 725-733; doi:10.1038/modpathol.2009 published online 6 March 2009 Keywords: endometrial; carcinoma; invasion; MELF; epithelial-mesenchymal transition; immunohistochemistry Endometrial carcinomas can be divided into two major groups on the basis of clinicopathological, immunohistological and molecular features. 1,2 The more common (type 1) subgroup accounts for 80-85% of cases and mainly comprises endometrioid adenocarcinomas of low-to-intermediate grade. These tumors typically occur in perimenopausal and younger postmenopausal patients, often arise in hyperestrogenic states and are associated with atypical endometrial hyperplasia/endometrial intraepithelial neoplasia. Frequently, type 1 carcinomas are confined to the uterine corpus at the time of diagnosis (stage 1), and the prognosis in such patients is generally ...

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Section: Discussionmentioning

confidence: 99%

Expression of cell cycle regulatory proteins in endometrial adenocarcinoma: variations in conventional tumor areas and in microcystic, elongated and fragmented glands

et al. 2009

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“…Overexpression of cyclin D1 in endometrial cancer has been reported in previous studies. [30][31][32] Our data showed, for the first time, that the loss of DACH1 expression is a frequent event in endometrial carcinoma, which may play an important role in endometrial carcinogenesis and malignant progression. Prognosis value of DACH1 and cyclin D1 in human endometrial carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Altered expression of DACH1 and cyclin D1 in endometrial cancer

Nan

Lü²,

Zhou³

et al. 2009

Cancer Biology & Therapy

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The altered expression of human DACH1, a Drosophila Dachshund homolog, has been associated with tumor progression and metastasis. DACH1 inhibits breast cancer cellular proliferation via cyclin D1. Endometrial cancer is the third most common cancer in women and broad screening for DACH1 expression will further our understanding of this disease. Herein, we screened 126 hysterectomy specimens for DACH1 expression and evaluated the correlation between DACH1 levels and several clinical parameters. Decreased DACH1 expression was significantly correlated with FIGO surgical stages (Stage I-II vs. stage III-IV, p = 0.017), peritoneal cytology (p = 0.044), lymph node positivity (p = 0.035) and histological type (p = 0.007), but not histological grade, depth of myometrial and patient age. Immunostaining was also conducted to examine the expression of cyclin D1, estrogen receptor alpha (ERα) and progesterone receptor (PR) in these specimens. Multivariate analysis using the stepwise Cox proportional hazard model showed that FIGO surgical stage, histological grade, lymph node metastasis, and PR expression were correlated with poor survival. Despite the fact that univariate analysis demonstrated that DACH1 positivity is associated with increased 5-year survival in all patients (p = 0.037), decreased expression of DACH1 had no significant value as an independent prognostic factor in predicting survival in endometrial cancers. Our results suggested that loss of DACH1 expression might be involved in endometrial cancer progression.

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“…We used HPV E6 and E7 as inhibitors of p53 and Rb function. Although genetic abnormality of the Rb locus, including loss of heterozygosity, or altered expression of Rb protein has not frequently been detected in endometrial cancer, alteration of the pathways upstream of Rb, such as aberrant expression of cyclinD1 and cdk4, has been observed in 60-70% of endometrial cancers (Niemann et al, 1997;Semczuk et al, 2004). Formation of a complex consisting of cyclinD1 and cdk4/6 induces Rb phosphorylation, resulting in activation of E2F, leading to cell cycle progression into the G1 phase.…”

Section: Creation Of Tumorigenic Endometrial Cells Y Mizumoto Et Almentioning

confidence: 99%

Creation of tumorigenic human endometrial epithelial cells with intact chromosomes by introducing defined genetic elements

Mizumoto

Kyo

Ohno³

et al. 2006

Oncogene

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Expression of the cell-cycle regulatory proteins (pRb, cyclin D1, p16INK4A and cdk4) in human endometrial cancer: correlation with clinicopathological features

Cited by 22 publications

References 38 publications

Expression of cell cycle regulatory proteins in endometrial adenocarcinoma: variations in conventional tumor areas and in microcystic, elongated and fragmented glands

Expression of cell cycle regulatory proteins in endometrial adenocarcinoma: variations in conventional tumor areas and in microcystic, elongated and fragmented glands

Altered expression of DACH1 and cyclin D1 in endometrial cancer

Creation of tumorigenic human endometrial epithelial cells with intact chromosomes by introducing defined genetic elements

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