Abstract
Carbohydrate expression of cancer cells is closely related to the metastatic nature of colorectal cancer. In the present study we investigated the relevance of carbohydrate expression profiles of colorectal cancer cells in the primary lesion to metastatic distribution patterns as well as prognosis in 134 cases. Carbohydrate expression was estimated by histochemistry with 17 kinds of lectins and 3 kinds of Lewis-related monoclonal antibodies (MAbs), and correlations between the staining and clinicopathological parameters were examined. The results showed that lymphatic invasion, lymph node metastasis, and peritoneal metastasis correlated with staining with lectins that bind galactose/N-acetylgalactosamine residues (Gal/GalNAc) such as Maclura pomifera (MPA), Arachis hypogaea (PNA), Helix pomatia (HPA), and Vicia villosa (VVA). In contrast, hepatic metastasis correlated with staining with Anguilla anguilla lectin (AAA), anti-LewisX (LEX-2), anti-sialyl Lewisa (NS19-9), and anti-sialyl-dimeric LewisX (FH-6) MAbs, all of which bind preferentially to fucosylated carbohydrate chains. The five-year survival rate of patients was related to the staining of cancers with MPA, HPA, FH-6 or NS19-9, and MPA- and FH-6 staining were independent prognostic factors. We conclude that carbohydrate expression profiles of cancer cells are relevant to the route of tumor cell dissemination, metastatic pattern as well as prognosis of colorectal cancer.
Similar content being viewed by others
References
Tsukuma H, Kitagawa T, Hanai A et al. Incidence of cancer prediction in Japan up to the year 2015. Gan-no-Rinsho 1992; 38: 1–10 [in Japanese].
Berge T, Ekelund G, Mellner C et al. Carcinoma of the colon and rectum in a defined population. An epidemiological, clinical and postmortem investigation of colorectal carcinoma and coexisting benign polyps in Malmo, Sweden. Acta Chirugica Scandinavica, Supplementum 1973; 438: 1–86.
Herter FP, Slanetz CA. Pattern and significance of lymphatic spread from cancer of the colon and rectum. In Weiss L, Gilbert HA, Ballon SC. (eds): Lymphatic System Metastasis. Boston: G.K. Hall Medical Publisher 1980; 275–307.
Mandai K, Saeki T, Yamagami K et al. Clinicopathological study of autopsy cases of colorectal carcinoma with hepatic metastases. Jpn J Cancer Clin 1995; 41: 252–8 [in Japanese].
Toribara NW, Ho SB, Bresalie RS et al. Biochemical changes in colorectal carcinogenesis. In Seitz HK, Simanowski NA, Wright NA (eds): Colorectal Cancer: From Pathogenesis to Prevention? Berlin: Springer-Verlag 1989; 256–88.
Hoff SD, Matsushita Y, Ota DM et al. Increased expression of sialyl-dimeric Lex antigen in liver metastases of human colorectal carcinoma. Cancer Res 1989; 49: 6883–8.
Matsushita Y, Clearly KR, Ota DM et al. Sialyl-dimeric Lewis-X antigen expressed on mucin-like glycoproteins in colorectal cancer metastases. Lab Invest 1990; 63: 780–91.
Nakagoe T, Fukushima K, Hirota M et al. Immunohistochemical expression of sialyl Lex antigen in relation to survival of patients with colorectal carcinoma. Cancer 1993; 72: 2323–30.
Nakamori S, Kameyama M, Imaoka S et al. Increased expression of sialyl Lewisx antigen correlates with poor survival in patients with colorectal carcinoma: Clinicopathological and immunohistochemical study. Cancer Res 1993; 53: 3632–7.
Irimura T, Nakamori S, Matsushita Y et al. Colorectal cancer metastasis determined by carbohydrate-mediated cell adhesion: Role of sialyl-LeX antigens. Semin Cancer Biol 1993; 4: 319–24.
Takabayashi T, Watanabe M, Sakurai Y et al. Western blot analysis of glycoproteins bearing Lewisa and sialyl-Lewisa antigens in human colorectal mucosa. J Surg Oncol 1993; 54: 91–7.
Nakayama T, Watanabe M, Katsumata T et al. Expression of sialyl Lewis (a) as a new prognostic factor for patients with advanced colorectal carcinoma. Cancer 1995; 75: 2051–156.
Nakamori S, Kameyama M, Imaoka S. Involvement of carbohydrate antigen sialyl Lewisx in colorectal cancer metastasis. Dis Colon Rectum 1997; 40: 420–31.
Itzkowitz SH, Yuan M, Montgomery CK et al. Expression of Tn, sialosyl-Tn, and T antigens in human colon cancer. Cancer Res. 1989; 49: 197–204.
Itzkowitz SH, Bloom EJ, Kokal WA et al. Sialyl-Tn. A novel mucin antigen associated with prognosis in colorectal cancer patients. Cancer 1990; 66: 1960–6.
Cao Y, Karsten U, Liebrich W et al. Expression of Thomsen-Friedenreich-related antigens in primary and metastatic colorectal carcinomas. Cancer 1995; 76: 1700–8.
Bresalier RS, Ho SB, Schoeppner HL et al. Enhanced sialylation of mucin-associated carbohydrate structures in human colon cancer metastasis. Gastroenterology 1996; 110: 1354–67.
Cao Y, Schlag PM, Karsten U. Immunodetection of epithelial mucin (MUC1, MUC3) and mucin-associated glycotopes (TF, Tn, and sialosyl-Tn) in benign and malignant lesions of colonic epithelium: Apolar localization corresponds tomalignant transformation. Virchow Arch 1997; 431: 159–66.
Imada T, Rino Y, Hatori S et al. Sialyl Tn antigen expression is associated with the prognosis with advanced colorectal cancer. Hepatogastroenterology 1999; 46: 208–14.
Morichika H, Hamanaka Y, Tai T et al. Sulfatides as a predictive factor of lymph nodes metastasis in patients with colorectal adenocarcinoma. Cancer 1996; 78: 43–7.
Mitchell BS, Schumacher U. The use of the lectin Helix pomatia agglutinin (HPA) as a prognostic indicator and as a tool in cancer research. Histol Histopathol 1999; 14: 217–26.
Schumacher U, Higgs D, Loizidou M et al. Helix pomatia agglutinin binding is a useful prognostic indicator in colorectal carcinoma. Cancer 1994; 74: 3104–7.
Ikeda Y, Mori M, Adachi Y et al. Prognostic value of the histochemical expression of Helix pomatia agglutinin in advanced colorectal cancer: a univariate and multivariate analysis. Dis Colon Rectum 1994; 37: 181–4.
Seelentag WK, Li WP, Schmit SF et al. Prognostic value of beta 1,6-branched oligosaccharides in human colorectal carcinoma. Cancer Res 1998; 58: 5559–64.
Brooks SA. The involvement of Helix pomatia lectin (HPA) binding N-acetylgalactosamine glycans in cancer progression. Histol Histopathol 2000; 15: 143–58.
Japanese Society for Cancer of the Colon and Rectum. General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus. Fifth edition, 1994.
Sobin LH and Wittekind Ch (eds): International Union Against Cancer (UICC), TNM Classification of Malignant Tumours, fifth edition. New York: A John Wiley & Sons, 1997.
Fenlon S, Ellis IO, Bell J et al. Helix pomatia and Ulex europeus lectin binding in human breast carcinoma. J Pathol 1987; 152: 169–76.
Hsu SM, Raine L, Fanger H. Use of avidin-biotin peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 1982; 29: 577–80.
Koyama S, Terashima S, Takano Y et al. P53 protein expression of carcinoma cells associated with metastasis and prognosis in gastric carcinomas: A Clinicopathological study. Fukushima Igaku Zasshi 1997; 47: 131–42 [in Japanese].
Kawaguchi T, Ono T, Wakabayashi H et al. Cell surface laminin-like substances and laminin-related carbohydrates of rat ascites hepatoma and its variants with different lung-colonizing potential. Clin Exp Metastasis 1994; 12: 203–12.
Macartney JC. Lectin histochemistry of galactose and N-acetylgalactosamine glycoproteins in normal gastric mucosa and gastric cancer and the relationship with ABO secretor status. J Pathol 1986; 150: 135–44.
Macartney JC. Fucose-containing antigens in normal and neoplastic human gastric mucosa: A comparative study using lectin histochemistry and blood group immunohistochemistry. J Pathol 1987; 152: 23–30.
Ohori T, Kawaguchi T. Carbohydrate expression of carcinoma cells associated with metastasis and prognosis in advanced gastric carcinomas: a clinicopathological study. Fukushima Igaku Zasshi 1998; 48: 25–36 [in Japanese].
Maehara Y, Okuyama T, Kakeji Y et al. A tumour-associated cellsurface glycoprotein accompanying p53 overexpression and higher growth potential for gastric cancer. Br J Cancer 1995; 71: 999–1002.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observation. J Am Stat Assoc 1958; 53: 457–81.
Cox DR. Regression models and life table. J R Stat Soci [B] 1972; 34: 187–220.
Lee X, Thompson A, Zhang Z et al. Structure of the complex of Maclura pomiferar agglutinin and the T-antigen disaccharide, Galbeta1, 3 GalNAc. J Biol Chem 1998; 273: 6312–8.
Hammarström S, Murphy LA, Goldstein IJ et al. Carbohydrate binding specificity of four N-acetyl-D-galactosamine-‘specific’ lectins: Helix pomatia A hemagglutinin, Soy bean agglutinin, Lima bean lectin, and Dolichos biflorus lectin. Biochemistry 1977; 16: 2750–5.
Tollefsen SE, Kornfeld R. The B4 lectin from Vicia villosa seeds interacts with N-acetylgalactosamine residues α-linked to serine or threonine residues in cell surface glycoproteins. J Biol Chem 1983; 258: 5172–6.
Schumacher U, Metchell BS, Brooks SA et al. Does the lectin Helix pomatia agglutinin bind to hyaluronic acid in breast and colon cancer? Acta Histochem 1996; 98: 435–40.
Wu AM, Song SC, Sugii S et al. Differential binding properties of Gal/GalNAc specific lectins available for characterization of glycoreceptors. Indian J Biochem Biophys 1997; 34: 61–71.
Killey C. Physicochemical properties and N-terminal sequence of eel lectin. Biochem J 1984; 220: 221–6.
Baldus SE, Thiele J, Park YO et al. Characterization of the binding specificity of Anguilla anguilla agglutinin (AAA) in comparison to Ulex europaeus agglutinin I (UEA-I). Glycoconju J 1996; 13: 585–90.
Kawaguchi T. Adhesion molecules and carbohydrates in cancer metastasis. Jpn J Clin Pathol 1996; 44: 1138–46 [in Japanese].
Iida S, Yamamoto K, Irimura T. Interaction of human macrophage Ctype lectin with O-linked N-acetylgalactosamine residues on mucin glycopeptides. J Biol Chem 1999; 274: 10697–705.
Irimura T, Denda K, Iida SI et al. Diverse glycosylation of MUC1 and MUC2: potential significance in tumor immunity. J Biochem 1999; 126: 975–85.
Rye PD, Fodstad Ø, Emilsten E et al. Invasion potential and Nacetylgalactosamine expression in a human melanoma model. Int J Cancer 1998; 75: 609–14.
Okuyama T, Maehara Y, Kakeji Y et al. Interaction between tumorassociated cell surface glycoprotein and host immune response in gastric carcinoma patients. Cancer 1998; 82: 1468–75.
Ye C, Kiriyama K, Mitsuoka C et al. Expression of E-selectin on endothelial cells of small veins in human colorectal cancer. Int J Cancer 1995; 61: 455–60.
Krause T, Turner GA. Are selectins involved in metastasis? Clin Exp Metastasis 1999; 17: 183–92.
Tomlinson J, Wang JL, Barsky SH et al. Human colon cancer cells express multiple glycoprotein ligands for E-selectin. Int J Oncol 2000; 16: 347–53.
Tabuchi Y, Deguchi H, Saitoh Y. Carcinoembryonic antigen and carbohydrate antigen 19-9 levels of peripheral and draining venous blood in colorectal cancer patients. Correlation with histopathologic and immunohistochemical variables. Cancer 1988; 62: 1605–13.
King MT, Chan A, Roe R et al. Two different glycosyltransferase defects that resut in GalNAc-O-peptide (Tn) expression. Glycobiol 1994; 4: 267–79.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Konno, A., Hoshino, Y., Terashima, S. et al. Carbohydrate expression profile of colorectal cancer cells is relevant to metastatic pattern and prognosis. Clin Exp Metastasis 19, 61–70 (2002). https://doi.org/10.1023/A:1013879702702
Issue Date:
DOI: https://doi.org/10.1023/A:1013879702702