epidermal-growth-factor and Carcinoma--Endometrioid

Epidermal and insulin-like growth factors (EGF, IGFs) act as mitogens promoting endothelial cell proliferation and differentiation. Accumulating evidence for interactions between EGF and IGF signaling pathways has been reported. Fibroblast growth factor-2 (FGF2) is also mitogenic for various cell types and is associated with regulation of tumor angiogenesis and metastasis. However EGF, IGF-1 and FGF2 transcript levels have been scarcely investigated in endometrial carcinoma.. In the present study, we evaluated the mRNA expression pattern of EGF, IGF-1 and FGF2 by using Comparative Quantitative real-time RT-PCR assay in 30 endometrial cancer specimens and an equal number of adjacent normal tissues.. Both overexpression and down-regulation of EGF, IGF-1 and FGF2 was demonstrated in endometrial cancer compared to the adjacent normal specimens; however the main features of cancer were IGF-1 and EGF down-regulation and FGF2 up-regulation. Different co-expression patterns of all three factors were displayed in normal and malignant endometrium. Interestingly, FGF2 mRNA was positively correlated with EGF and IGF-1 transcript levels in endometrial cancer (P=0.024 and P=0.006, respectively), while no co-expression was observed in the adjacent normal specimens. Furthermore, endometrial tissue-pair analysis revealed a significant positive correlation between EGF and IGF-1 (P=0.010), supporting the hypothesis of a cross-talk between IGF- and EGF-mediated signaling pathways in endometrial cancer. EGF transcript levels were marginally higher in endometrioid than non-endometrioid tumors (P=0.050), and in grade I compared to grade II tumors (P=0.053).. Up-regulation as well as down-regulation of EGF, IGF-1 and FGF2 transcript levels is observed in endometrial cancer; however IGF-1 and EGF down-regulation and FGF2 up-regulation seem to comprise the main features of endometrial carcinogenesis. The disruption of their mRNA co-expression pattern observed supports the hypothesis of a cross-talk between IGF- and EGF-mediated signaling pathways in promoting endothelial cell proliferation and differentiation in endometrial cancer.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Endometrioid; Down-Regulation; Endometrial Neoplasms; Endometrium; Epidermal Growth Factor; Female; Fibroblast Growth Factor 2; Gene Expression Regulation, Neoplastic; Humans; Insulin-Like Growth Factor I; Middle Aged; Polymerase Chain Reaction; RNA, Messenger; Up-Regulation

The Epidermal Growth Factor (EGF) system is expressed in healthy premenopausal endometrium. We describe the expression of the four receptors, HER1, HER2, HER3, HER4 and the six ligands amphiregulin, transforming growth factor alpha (TGF-alpha), heparin binding EGF like growth factor (HB-EGF), betacellulin, epiregulin and EGF in endometrioid endometrial cancer.. We have uterine samples from 45 women with endometrioid endometrial cancer. As normal counterparts, endometrial samples from thirteen postmenopausal women, and previous data on fourteen premenopausal women were employed. Extracted RNA was analyzed by real-time PCR; the receptors and ligands were localized by immunohistochemistry.. Three receptors (HER1, HER2 and HER4) and two detectable ligands (TGF-alpha and HB-EGF) are expressed significantly higher in endometrial cancer than in healthy postmenopausal endometrium. Cancer tissue show significantly lower expression of HER1 and HER3, and higher expression of HER4, amphiregulin, TGF-alpha and HB-EGF compared to premenopausal endometrium; no difference is seen in HER2. EGF is undetectable in all of the samples. Immunohistochemically the receptors locate to the epithelium and/or glands while the ligands locate to the stroma (amphiregulin), the stroma and the epithelium (TGF-alpha, epiregulin), the epithelium (betacellulin) or are not detectable (HB-EGF, EGF).. mRNA of all receptors and five ligands are present in endometrioid endometrial cancer, and the protein of all receptors and four ligands are identified by immunohistochemistry. The expression pattern in endometrioid endometrial cancer differs from the pattern in pre- and postmenopausal endometrium. The most remarkable finding is an increased level of HER4, a receptor which correlates to a favorable prognosis in other types of cancers.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Endometrioid; Endometrial Neoplasms; Epidermal Growth Factor; ErbB Receptors; Female; Humans; Immunohistochemistry; Middle Aged; RNA, Messenger

The aim of our study was to describe the expression of cerbB-1, cerbB-2, cerbB-3 and cerbB-4 in endometrial cancer tissue and its correlation with clinicopathologic features and prognosis of endometrial cancer patients diagnosed during or after tamoxifen treatment for breast cancer. Thirteen tamoxifen-related endometrial cancers were identified from the archives of the Department of Obstetrics and Gynecology of the University of Patras, Medical School. Tissue specimens from endometrial lesions were immunostained for cerbB-1, cerbB-2, cerbB-3 and cerbB-4. For cerbB-1, five cases were positive and eight were negative. For cerbB-2, ten cases were positive and three were negative. For cerbB-3, nine cases were positive and four were negative. For cerbB-4, eight cases were positive and five were negative. However, a limitation of our study is that the number of cases was small, and further investigations are necessary to allow a more focused evaluation of cerbB-1, cerbB-2, cerbB-3 and cerbB-4 status, as a prognostic factor for endometrial cancer after tamoxifen treatment.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Breast Neoplasms; Carcinoma, Endometrioid; Chemotherapy, Adjuvant; Endometrial Neoplasms; Epidermal Growth Factor; Female; Humans; Middle Aged; Neoplasm Staging; Postmenopause; Tamoxifen

The biological significance of epidermal growth factor (EGF)-related proteins in the development and progression of endometrioid endometrial carcinoma was studied. Expression of EGF-related proteins including EGF, transforming growth factor-alpha (TGF-alpha), cripto (CR), amphiregulin (AR), and EGF receptor (EGFR) were immunohistochemically examined. Results were then correlated with clinicopathologic findings and steroid receptor status in 12 specimens with normal endometrium, 13 with endometrial hyperplasia, and 40 with endometrioid endometrial carcinoma. EGFR, EGF, TGF-alpha, and CR immunoreactivities were observed in 58.3%, 66.7%, 91.6%, and 66.7% of normal endometrial specimens; 100%, 15.4%, 100%, and 30.8% of endometrial hyperplasia specimens; and 67.5%, 32.5%, 65.0%, and 65.0% of endometrial carcinoma specimens, respectively. AR immunoreactivity was not observed in any of the normal, hyperplastic, or neoplastic endometrium. The presence or absence of EGFR or TGF-alpha in endometrial carcinoma correlated with surgical stage, depth of myometrial invasion, and findings from peritoneal washing cytology. EGF expression significantly correlated with the age of the patients and that of CR with surgical stage and peritoneal washing cytological findings. There was a significant correlation between EGFR and TGF-alpha expression, and between EGF and TGF-alpha. Co-expression of EGFR and TGF-alpha, EGFR and CR, and TGF-alpha and CR in carcinoma specimens significantly correlated with advanced surgical stage, deeper myometrial invasion, and positive peritoneal washing cytology. In normal as well as hyperplastic endometrium, endometrial glands immunohistochemically positive for TGF-alpha were generally positive for ER, but in poorly differentiated endometrial carcinoma, cells positive for TGF-alpha tended to be negative for ER. The results of the present study show that among EGF-related proteins, expression of TGF-alpha and CR seem to be associated with the progression of human endometrioid endometrial carcinoma. Additionally, expression of TGF-alpha became increasingly estrogen independent with increasing histological carcinoma grades.

Topics: Adult; Amphiregulin; Carcinoma, Endometrioid; EGF Family of Proteins; Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Epidermal Growth Factor; ErbB Receptors; Female; Glycoproteins; GPI-Linked Proteins; Growth Substances; Humans; Intercellular Signaling Peptides and Proteins; Membrane Glycoproteins; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Receptors, Estrogen; Receptors, Progesterone; Receptors, Steroid; Retrospective Studies; Transforming Growth Factor alpha

Sex steroid hormone dependent cell proliferation and inducing growth factors of endometrial carcinoma cells were investigated using in vitro culture systems. The cell proliferation of Ishikawa cells derived from well-differentiated endometrial adenocarcinoma which possess both estrogen and progesterone receptors were stimulated by either estradiol added to culture media or EGF and TGF-alpha acting through EGF receptors. These stimulatory effects of TGF-alpha were antagonized by the anti TGF-alpha and EGF-receptor antibodies. The cell proliferations of other endometrial cancer cells were also inhibited by those antibodies. All endometrial cancer cells secrete TGF-alpha into their culture media measured by TGF-alpha ELISA methods. The expression of TGF-alpha mRNA and secretion of TGF-alpha of Ishikawa cells were induced by estradiol but not of hormone independent HEC-50 cells. Thus suggest that estradiol dependent growth factor should be TGF-alpha in human endometrial carcinoma cells.

Topics: Carcinoma, Endometrioid; Cell Division; Epidermal Growth Factor; ErbB Receptors; Estradiol; Female; Humans; Neoplasms, Hormone-Dependent; Receptors, Estrogen; Receptors, Progesterone; RNA, Messenger; Transforming Growth Factor alpha; Tumor Cells, Cultured; Uterine Neoplasms