title: Overexpression of Id-1 is associated with poor clinical outcome in node negative breast cancer.
abstract: Id-1 is an important regulator of cellular growth and differentiation and controls malignant progression of breast cancer cells. The aim of our study was to assess the clinical impact of Id-1 expression in breast cancer, i.e., its potential impact on prognosis and prediction of treatment response. Id-1 protein expression was determined immunohistochemically in 191 patients with lymph-node negative breast cancer, and univariate and multivariate survival analysis was carried out. Fifteen (7.9%) specimens showed strong expression, 75 (39.3%) moderate, 55 (28.8%) weak expression and 46 (24.1%) cases no expression of Id-1. Patients with strong or moderate Id-1 expression had a significant shorter overall (p = 0.003, Cox regression) and disease-free survival (p = 0.01, Cox regression) compared to those with absent or low expression. Progesterone receptor density was significantly higher in breast cancers with absent/low Id-1 expression compared to those with moderate/strong expression (p < 0.001, t-test). Id-1 expression was significantly stronger in cases positive for p16(INK4a) expression compared to those negative for p16 (p = 0.049, Mann-Whitney test). The influence of Id-1 on clinical outcome seems much stronger in patients with negative estrogen receptor status compared to those with positive status, who received receptor antagonists as adjuvant therapy in most cases. Overexpression of Id-1 protein represents a strong independent prognostic marker in node negative breast cancer, and future therapies inhibiting Id-1 expression might be beneficial for these patients. Our results also suggest that due to the apparent interaction of Id-1 with the steroid-receptor system in breast cancer, hormonal therapies might influence Id-1 expression and its impact on clinical outcome.
authors.affiliation: Department of Surgery, University of Vienna, Vienna, Austria.
authors.forename: Sebastian F
authors.initials: SF
authors.lastname: Schoppmann
authors.forename: Monika
authors.initials: M
authors.lastname: Schindl
authors.forename: Guenther
authors.initials: G
authors.lastname: Bayer
authors.forename: Klaus
authors.initials: K
authors.lastname: Aumayr
authors.forename: Julia
authors.initials: J
authors.lastname: Dienes
authors.forename: Reinhard
authors.initials: R
authors.lastname: Horvat
authors.forename: Margaretha
authors.initials: M
authors.lastname: Rudas
authors.forename: Michael
authors.initials: M
authors.lastname: Gnant
authors.forename: Raimund
authors.initials: R
authors.lastname: Jakesz
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005260:Female; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D007124:Immunoenzyme Techniques; D051798:Inhibitor of Differentiation Protein 1; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012097:Repressor Proteins; D015996:Survival Rate; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D012097:Repressor Proteins; D014157:Transcription Factors