Prognostic Value of ß1,6-Branchecl Oligosaccharides in Human Colorectal Carcinoma1

Increase of ßl,6-branched Oligosaccharides is possibly associated with tumor progression and lymph node metastasis. The aim of this study was to determine the prognostic value of /{!,(> branches in human colorectal carcinoma. Expression of /!!,(> branches was histochemically evaluated using the leukoagglutinating Phaseolus vulgaris lectin, PHA-L, in 92 clin ically documented colorectal carcinomas, of which 31 had formed lymph node métastases. The follow-up time ranged between 4 and 14 years (median, 10.3 years). A PHA-L staining index (SI), taking into account staining intensity and its percentage of tumor cut surface area, was established. The carcinoma SI was highly associated with the disease-free survival I/' = 0.004) and overall survival (P = 0.005). Patients with a carcinoma SI of >1, as compared to those with a SI of ¿1, were at significantly higher risk for tumor recurrence, with a shorter disease-free survival (hazard ratio = 2.59, /* = 0.005) and significant higher risk of death with shorter overall survival (hazard ratio = 2.51, P = 0.007). The carcinoma SI was also associated with the presence of lymph node mé tastases. We conclude that PHA-L staining in human colorectal carcinoma sections provides an independent prognostic indicator for tumor recur rence and patient survival and is associated with the presence of lymph node métastases.

[1]  D. Carter.  TNM Classification of Malignant Tumors , 1998 .

[2]  Wei-ping Li,et al.  Expression of beta 1,6 branched asparagine‐linked oligosaccharides in non‐mitotic and non‐migratory cells of normal human and rat tissues , 1997, International journal of cancer.

[3]  S. Hakomori.  Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. , 1996, Cancer research.

[4]  J. Dennis,et al.  GlcNAc-transferase V and core 2 GlcNAc-transferase expression in the developing mouse embryo. , 1995, Glycobiology.

[5]  J. Dennis,et al.  Reduced contact-inhibition and substratum adhesion in epithelial cells expressing GlcNAc-transferase V , 1995, The Journal of cell biology.

[6]  N. Fregien,et al.  Expression of N-acetylglucosaminyltransferase V mRNA in mammalian tissues and cell lines. , 1994, Glycobiology.

[7]  Wei-ping Li,et al.  Use of Phaseolus vulgaris leukoagglutinating lectin in histochemical and blotting techniques: a comparison of digoxigenin- and biotin-labelled lectins , 1993, Histochemistry.

[8]  P. Goss,et al.  A phase I study of swainsonine in patients with advanced malignancies. , 1993, Cancer research.

[9]  J. W. Dennis,et al.  N-linked oligosaccharide processing and autocrine stimulation of tumor cell proliferation. , 1991, Experimental cell research.

[10]  J. Dennis,et al.  Beta 1-6 branched oligosaccharides as a marker of tumor progression in human breast and colon neoplasia. , 1991, Cancer research.

[11]  J. Dennis,et al.  Growth inhibition of human melanoma tumor xenografts in athymic nude mice by swainsonine. , 1990, Cancer research.

[12]  J. Dennis,et al.  Oncogenes conferring metastatic potential induce increased branching of Asn-linked oligosaccharides in rat2 fibroblasts. , 1989, Oncogene.

[13]  J. Dennis,et al.  Oncodevelopmental Expression of —GlcNAcβ1–6Manα1-6Manβ1— Branched Asparagine-linked Oligosaccharides in Murine Tissues and Human Breast Carcinomas , 1989 .

[14]  W. Dijk,et al.  Effect of α(2–6)-linked sialic acid and α(1–3)-linked fucose on the interaction ofN-linked glycopeptides and related oligosaccharides with immobilizedPhaseolus vulgaris leukoagglutinating lectin (L-PHA) , 1988, Glycoconjugate Journal.

[15]  J. Jass,et al.  A NEW PROGNOSTIC CLASSIFICATION OF RECTAL CANCER , 1987, The Lancet.

[16]  R. Kerbel,et al.  Beta 1-6 branching of Asn-linked oligosaccharides is directly associated with metastasis. , 1987, Science.

[17]  J. Dennis.  Effects of swainsonine and polyinosinic:polycytidylic acid on murine tumor cell growth and metastasis. , 1986, Cancer research.

[18]  J. Cuzick,et al.  The grading of rectal cancer: historical perspectives and a multivariate analysis of 447 cases , 1986, Histopathology.

[19]  M. Humphries,et al.  Oligosaccharide modification by swainsonine treatment inhibits pulmonary colonization by B16-F10 murine melanoma cells. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[20]  A. Kobata,et al.  Enzymatic basis for the structural changes of asparagine-linked sugar chains of membrane glycoproteins of baby hamster kidney cells induced by polyoma transformation. , 1985, The Journal of biological chemistry.

[21]  A. Kobata,et al.  Comparative study of the oligosaccharides released from baby hamster kidney cells and their polyoma transformant by hydrazinolysis. , 1984, The Journal of biological chemistry.

[22]  R. Cummings,et al.  Characterization of the structural determinants required for the high affinity interaction of asparagine-linked oligosaccharides with immobilized Phaseolus vulgaris leukoagglutinating and erythroagglutinating lectins. , 1982, The Journal of biological chemistry.

[23]  D. Tulsiani,et al.  Swainsonine inhibits the biosynthesis of complex glycoproteins by inhibition of Golgi mannosidase II. , 1982, The Journal of biological chemistry.

[24]  R. S. Grinnell.  THE GRADING AND PROGNOSIS OF CARCINOMA OF THE COLON AND RECTUM , 1939, Annals of surgery.

[25]  Cuthbert Dukes,et al.  Histological Grading of Rectal Cancer , 1937 .

[26]  T. Sata,et al.  Lectin-Gold Histochemistry on Paraffin and Lowicryl K4M Sections Using Biotin and Digoxigenin-Conjugated Lectins. , 1998, Methods in molecular medicine.

[27]  K. Olden,et al.  The potential importance of swainsonine in therapy for cancers and immunology. , 1991, Pharmacology & therapeutics.