transforming-growth-factor-alpha and Carcinoma--Lobular

The aim of this study is to provide an expression profile of ErbB/HER ligands in breast cancer. We analysed the relationships with their receptors, the bio-pathological features and prognosis.. Epidermal growth factor (EGF), transforming growth factor-alpha (TGFalpha), amphiregulin (AREG), betacellulin (BTC), heparin-binding EGF-like growth factor (HB-EGF), epiregulin (EREG) and neuregulins1-4 (NRG1-4) were quantified in 363 tumours by real-time reverse transcription-polymerase chain reaction using TaqMan probes.. Ligands were detected in 80%-96% of the cases, except NRG3 (42%) and EREG (45.5%). At least one ligand was expressed in 304 cases (cut-off: upper quartile). Almost all combinations of receptor and ligand co-expressions were observed, but TGFalpha is preferentially expressed in tumours co-expressing EGFR/HER3, NRG3 in those co-expressing EGFR/HER4, AREG and EREG in those co-expressing HER2/HER4. EGF and AREG were associated with estradiol receptors, small tumour size, low histoprognostic grading, high HER4 levels. TGFalpha, HB-EGF and NRG2 were negatively related to these parameters. In Cox univariate analyses, EGF was a prognostic factor.. Our study demonstrates that (i) ErbB/HER ligands, including BTC and EREG, are expressed in most breast cancers; and (ii) TGFalpha, HB-EGF and NRG2 high expressions are related to the biological aggressiveness of the tumours.

Topics: Amphiregulin; Betacellulin; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Disease-Free Survival; EGF Family of Proteins; Epidermal Growth Factor; Epiregulin; ErbB Receptors; Female; Gene Expression Profiling; Glycoproteins; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins; Neoplasm Invasiveness; Neoplasm Proteins; Nerve Growth Factors; Nerve Tissue Proteins; Neuregulin-1; Neuregulins; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; RNA, Messenger; RNA, Neoplasm; Transforming Growth Factor alpha

Hypoxia-inducible factor-1 (HIF-1) is the key transcription factor regulating the cellular response to hypoxia, including angiogenesis. Growth factors play an important role in tumour growth and angiogenesis and some have been shown to be induced by HIF-1 in vitro. This study investigated if angiogenesis or growth factors or their receptors are associated with HIF-1alpha in invasive breast cancer.. High levels of HIF-1alpha, detected by immunohistochemistry in 45 breast cancers, were positively associated with increased microvessel density (as a measure of angiogenesis) (P = 0.023). Furthermore, high levels of HIF-1alpha were associated with epithelial expression (> or = 10%) of epidermal growth factor receptor (EGFR) (P = 0.011), platelet-derived growth factor (PDGF)-BB (P < 0.001), and basic fibroblast growth factor (bFGF) (P = 0.045). A positive, yet insignificant, trend for HIF-1alpha to be associated with epithelial expression of transforming growth factor (TGF)-alpha (P = 0.081) and vascular endothelial growth factor (VEGF) (P = 0.109) was noticed as well as an inverse association with stromal expression of TGF-beta-R1 (P = 0.070).. In invasive breast cancer, HIF-1alpha is associated with angiogenesis, and expression of growth factors bFGF and PDGF-BB, and the receptor EGFR. Thus, agents targeting HIF-1 may combine different pathways of inhibiting breast cancer growth, including angiogenesis and growth factors.

Topics: Autocrine Communication; Becaplermin; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Epithelial Cells; ErbB Receptors; Eukaryotic Initiation Factor-3; Female; Fibroblast Growth Factor 2; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Lymph Nodes; Neoplasm Invasiveness; Neovascularization, Pathologic; Platelet-Derived Growth Factor; Proteins; Proto-Oncogene Proteins c-sis; Stromal Cells; Transcription Factors; Transforming Growth Factor alpha; Vascular Endothelial Growth Factor A

A pilot study of a novel translational research method to simultaneously assay multiple molecular markers and DNA in fine-needle aspirates (FNA) of mammographically detected breast lesions is described. Specimen mammography-guided 20-gauge FNAs obtained from 86 lesions and 22 areas of normal tissue were analyzed by multiparameter flow cytometry for DNA content, her2/neu, transforming growth factor alpha (TGF alpha), and the epithelial marker cytokeratin (CK) simultaneously. Epithelial cell her2/neu positivity was detected in 12 of 44 (27%) of invasive ductal carcinomas and 3 of 9 (33%) ductal carcinoma in situ (DCIS), 10 of 30 (33%) benign lesions, and 4 of 22 (18%) normal tissue aspirates. All lesions and normal tissue showed a similar positive rate for TGFalpha ranging from 61 to 76%. The CK(+)TGF alpha(-)her2/neu(+) immunophenotype was more frequently positive in aneuploid tumors (22%) than all other lesions (7%) (P < 0.05). Specimen mammography-guided FNAs provide fresh cells for flow cytometric multiple marker analysis and immunophenotyping of clinically occult breast lesions and normal tissue.

Topics: Adult; Aged; Aged, 80 and over; Aneuploidy; Biomarkers, Tumor; Biopsy, Needle; Breast; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Diploidy; DNA; Female; Flow Cytometry; Humans; Immunophenotyping; Keratins; Mammography; Middle Aged; Pilot Projects; Receptor, ErbB-2; Transforming Growth Factor alpha

Localization of growth factors such as transforming growth factor alpha (TGF-alpha) and beta1 (TGF-beta1), insulin-like growth factor 1 (IGF-1), and epidermal growth factor receptor (EGFR) in breast cancer tissue is controversial. We immunohistochemically investigated expression patterns of these growth factors and EGFR along with estrogen receptor (ER) status in 36 breast carcinomas (21 invasive ductal, 11 invasive lobular, 4 noninvasive ductal) and compared the results with those found in 10 fibroadenomas. Twenty-four of 36 carcinomas and all of the 10 fibroadenomas showed positivity for ER. TGF-alpha was immunoreactive in all of the carcinomas and fibroadenomas. TGF-beta1 was negative in all of the invasive ductal carcinomas and positive in all of the fibroadenomas and in five lobular carcinomas. EGFR was regularly expressed preferentially in the myoepithelial cells of mammary ducts in the fibroadenomas and in nontumorous glands. Six of the 36 carcinomas were positive for EGFR. Those tumors were negative for ER (P < .001). There was IGF-1 expression in all of the cases of carcinoma and fibroadenoma. We conclude that TGF-alpha is expressed abundantly in invasive and intraductal breast carcinomas and in fibroadenomas. EGFR expression significantly correlates with negative ER status in breast carcinoma. In breast carcinoma, IGF-1 is broadly expressed by the tumor as well as by stromal cells and might act as a growth stimulator in endocrine, paracrine, and autocrine manners.

Topics: Adenocarcinoma; Adult; Aged; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; ErbB Receptors; Female; Fibroadenoma; Humans; Immunohistochemistry; Insulin-Like Growth Factor I; Middle Aged; Transforming Growth Factor alpha; Transforming Growth Factor beta