title: Prognostic significance of reduced expression of beta-N-acetylgalactosaminylated N-linked oligosaccharides in human breast cancer.
abstract: Our previous studies showed that expression of the GalNAcbeta1-->4GlcNAc group on N-linked oligosaccharides is associated with functional differentiation of the bovine mammary gland. In the present study, the occurrence of the GalNAcbeta1-->4GlcNAc group was established in human milk proteins and membrane glycoproteins from a human breast cancer cell line, MRK-nu-1, by structural analysis of oligosaccharides released by hydrazinolysis. Whether the expression level of the disaccharide group is affected upon malignant transformation was examined in human breast cancer specimens using Wistaria floribunda agglutinin (WFA) which interacts with oligosaccharides with N-acetylgalactosamine at their termini. Lectin blot analysis of membrane glycoprotein samples from human breast cancer specimens showed that the number of protein bands reacting with WFA, as well as their intensities, are lower in samples from primary carcinoma lesions compared with samples from surrounding normal tissues. No lectin binding was observed when the blots were treated with jack bean beta-N-acetylhexosaminidase or N-glycanase, indicating that WFA-reactive oligosaccharides are N-linked. A histochemical study of tissue specimens from 92 patients with breast cancer revealed that the reduced WFA staining levels in primary carcinoma lesions correlate with advancing clinical stages and prognostic status (i.e., 58% of patients in a group showing reduced/negative staining died of disease recurrence, whereas more than 90% of those in the positive staining group survived for 5 years after surgery). These results indicate that reduced expression of beta-N-acetylgalactosaminylated N-linked oligosaccharides on primary carcinoma lesions predicts a poor prognosis for patients with breast cancer.
authors.affiliation: Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kitamura
authors.forename: Shanchun
authors.initials: S
authors.lastname: Guo
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sato
authors.forename: Sen
authors.initials: S
authors.lastname: Hiraizumi
authors.forename: Junko
authors.initials: J
authors.lastname: Taka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ikekita
authors.forename: Shuzo
authors.initials: S
authors.lastname: Sawada
authors.forename: Hirosuke
authors.initials: H
authors.lastname: Fujisawa
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D004187:Disaccharides / Q000378:metabolism*; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry; D037121:Plant Lectins / Q000378:metabolism; D034781:Receptors, N-Acetylglucosamine; D014407:Tumor Cells, Cultured
chemical_list: D004187:Disaccharides; D008562:Membrane Glycoproteins; D037121:Plant Lectins; D034781:Receptors, N-Acetylglucosamine; C040129:wisteria lectin; C042746:N-acetylgalactosaminyl-(1-4)-glucose