MUC1 mucin and carbohydrate associated antigens as tumor markers in head and neck squamous cell carcinoma

  • Maria V. Croce
  • Martin E. Rabassa
  • Mike R. Price
  • Amada Segal-Eiras


An immunological analysis to study MUC1 mucin core protein and carbohydrate associated antigens as tissue tumor markers in head and neck carcinoma was performed. Twenty nine patients with the following tumor localizations were included: tongue (n=10), larynx (n=8), oral cavity (n=4), maxillary sinus (n=3), tonsillar ring (n=3) and pharynx (n=1); seven samples of epithelium obtained from normal organs at the same localizations were studied as controls. Immunohistochemical analysis was performed following standard procedures and reaction was graded according to staining intensity and distribution. From each tissue section, membrane, cytoplasmic and nuclear moieties were obtained by differential centrifugation with subsequent fractionation by density gradient centrifugation (6M guanidium chloride-CsCl); subcellular moieties and CsCl derived fractions were analyzed by immunoblotting. Monoclonal antibodies (MAbs) reacting with the core protein of MUCI (C595) and associated carbohydrate antigens were: Tn, 83D4 MAb; Lewis y antigen (Le y), C14 MAb; Lewis x antigen (Le x), KM380 MAb and sialyl Lewis x (sLe x), KM93 MAb. Statistical analysis was undertaken by Spearman rank correlation. In tumor samples, the immunohis-tochemical identification of MUCl core protein and associated antigens was extended; differences were found in the pattern and intensity of expression; results were corroborated by immunoblotting although in a few samples there was not coincidence between both methods. Localization, tumor mass or node involvement did not show significant differences for any of the antigens studied. Conclusions: 1) head and neck carcinoma expressed MUCI and associated carbohydrate antigens in high levels; 2) no relationship between antigenic expression and tumor status was found.


Head and Neck Squamous Cell Carcinoma (HNSCC) MUCI mucin carbohydrate associated antigens 


  1. 1.2
    Brakenhoff RH, Stroomer JGW, den Brink C, et al: Sensitive detection of squamous cells in bone marrow and blood of head and neck cancer patients by E48 reverse transcriptase polymerase chain reaction. Clin Cancer Res 5:725–732, 1999.PubMedGoogle Scholar
  2. 2.2
    Brennan JA, Mao L, Hruban RH, et al: Molecular assessment of histopathological staging in squamous cell-carcinoma of the head and neck. N Engl J Med 332:429–435, 1995.PubMedCrossRefGoogle Scholar
  3. 3.2
    Brown A, Feizi T, Gooi HC: A monoclonal antibody against human colonic adenoma recognises a difucosylated type-2 blood group chains. Biosci Rep 3:163–169, 1983.PubMedCrossRefGoogle Scholar
  4. 4.2
    Burchell J, Durbin H, Taylor-Papadimitriou J: Complexity of expression of antigenic determinants recognised by monoclonal antibodies HMFG-1 and HMFG-2 in normal and malignant human mammary epithelial cells. J Immunol 131:508–513, 1983.PubMedGoogle Scholar
  5. 5.2
    Croce MV, Price MR, Segal-Eiras A: Expression of monoclonal antibody-defined antigens in fractions isolated from human breast carcinoma and patients’ serum. Cancer Immunol Immunother 40:132–137, 1995.PubMedCrossRefGoogle Scholar
  6. 6.2
    Croce MV, Colussi AG, Price MR, et al: Immunohistopathological characterization of spontaneous metastases in a human lung mucoepidermoid adecarcinoma (HLMC) xenograft. Pathol Oncol Res 4:259–266, 1998.PubMedCrossRefGoogle Scholar
  7. 7.2
    Croce MV, Price MR, Segal-Eiras A: Detection and isolation of MUC 1 mucin from larynx squamous cell carcinoma. Pathol Oncol Res 2:93–99, 2000.CrossRefGoogle Scholar
  8. 8.2
    Federici MF, Kudryashov V, Saigo P, et al: Selection of carbohydrte antigens in human epithelial ovarian cancers as targets for immunotherapy: serous and mucinous tumors exhibit distinctive patterns of expression. Int J Cancer 81:193–198, 1999.PubMedCrossRefGoogle Scholar
  9. 9.2
    Feickert HJ, Anger BR, Cordon-Cardo C, et al: Cell-surface antigens of human lung tumors detected by mouse monoclonal antibodies: definition of blood-group-and non-blood-group-related antigenic systems. Int J Cancer 46: 1007–1013, 1990.PubMedCrossRefGoogle Scholar
  10. 10.2
    Fukuda M: Possible roles of tumor-associated carbohydrate antigens. Cancer Res 56:2237–2244, 1996.PubMedGoogle Scholar
  11. 11.2
    Gendler SJ, Spicer AP: Epithelial mucin genes. Ann Rev Physiol 57:607–634, 1995.CrossRefGoogle Scholar
  12. 12.2
    Griffiths A, Burchell J, Gendler S, et al: Immunological analysis of mucin molecules expressed by normal and malignant epithelial cells. Int J Cancer 40:319–327, 1987.PubMedCrossRefGoogle Scholar
  13. 13.2
    Hanai N, Shitara K, Yoshida H: Generation of monoclonal antibodies against human lung squamous cell carcinoma and adenocarcinoma using mice rendered tolerant to normal human lung. Cancer Res., 46:4438–4443, 1986.PubMedGoogle Scholar
  14. 14.2
    Hakomori S: Aberrant glycosylation in cancer cell membranes as focused on glycolipids: overview and perspectives. Cancer Res. 45:2406–2414, 1985.Google Scholar
  15. 15.2
    Hilkens J, Ligtenberg JL, Vos HL, Litvinov S: Cell membrane-associated mucins and their adhesion-modulating property. Trends Biochem Sci 1992; 17:359–63, 1992.PubMedCrossRefGoogle Scholar
  16. 16.2
    Ikeda Y, Kuwano H, Ikebe M, et al: Immunohistochemical detection of CEA, CA19-9 and DF3 in esophageal carcinoma limited to the submucosal layer. J Sur Oncol 56:7–12, 1994.CrossRefGoogle Scholar
  17. 17.2
    International Union Against cancer (UICC) Classification of Malignant tumors. ED.L.H. Sobin and Ch. Wittekind, 5th edition, New York, 1997.Google Scholar
  18. 18.2
    Ioannides CG, Fisk B, Jerome KR, Irimura T: Cytotoxic T cells from ovarian malignant tumors can recognize polymorphic epithelial mucin core peptides. J Immunol 151:3693–3703, 1993.PubMedGoogle Scholar
  19. 19.2
    Itoh T, Yonezawa S, Nemoto M et al: expression of mucin antigen and Lewis x-related antigens in carcinoma s and dysplasia of the pharynx and larynx. Pathol Int 46: 646–655, 1996.PubMedCrossRefGoogle Scholar
  20. 20.2
    Jeannon JP, Stafford FW, Soames JV, Wilson JA: Altered MUC1 and MUC2 glycoprotein expression in laryngeal cancer. Otolaryngol Head and Neck Surg 124:199–202, 2001.CrossRefGoogle Scholar
  21. 21.2
    Jerome KR, Barnd DL, Bendt KM: Cytotoxic T-lymphocytes derived from patients with breast adenocarcinoma recognize an epitope present on the protein core of a mucin molecule prefer-entially expressed by malignant cells. Cancer Res 5:2908–2916, 1991.Google Scholar
  22. 22.2
    Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature (Lond) 227:680–681, 1980.CrossRefGoogle Scholar
  23. 23.2
    Nakagoe T, Sawai T, Tsuji T, et al: Preoperative serum levels of sialyl Lewis (a), sialyl Lewis(x) and sialyl Tn antigens as prognostic markers after curative resection for colorectal cancer. Cancer Detect Prev 25:299–308, 2001.PubMedGoogle Scholar
  24. 24.2
    Nakamori S, Kameyama M, Imaoka S, et al: Involvement of carbohydrate antigen sialyl Lewis x in colorectal cancer metastasis. Dis Colon Rectum 40:420–431, 1997.PubMedCrossRefGoogle Scholar
  25. 25.2
    Nitta T, Sugihara K, Tsuyama S et al: Immunohistochemical study of MUC1 mucin in premalignant oral lesions and oral squamous cell carcinoma. Cancer 88:245–254, 2000.PubMedCrossRefGoogle Scholar
  26. 26.2
    Pancíno GF, Osinaga E, Vorauher W, et al: Production of a monoclonal antibody as immunohistochemical marker on paraffin embedded tissues using a new immunization method. Hybridoma 9:389, 1990.PubMedCrossRefGoogle Scholar
  27. 27.2
    Price MR, Edwards S, Owainati A, et al: Multiple epitopes on a human breast carcinoma associated antigen. Int J Cancer 36:567, 1985.PubMedCrossRefGoogle Scholar
  28. 28.2
    Price MR, Pugh J, Hudecz F, O’Sullivan, C et al: Immunological and structural features of the protein core of human polymorphic epithelial mucin. Mol Immunol 27:795–801, 1990.PubMedCrossRefGoogle Scholar
  29. 29.2
    Regimbald LH, Pilarski LM, Longenecker BM: The breast mucin MUC1 as a novel adhesion ligand for endothelial intercellular adhesion molecule 1 in breast cancer. Cancer Res 56:4244–4249, 1996.PubMedGoogle Scholar
  30. 30.2
    Rubin JS, Bloor BK, Hart IR, Morgan PR: Muo-1 gene expression in head and neck squamous cell carcinoma. J Laryngol Otol 114:772–776, 2000.PubMedCrossRefGoogle Scholar
  31. 31.2
    Svitacheva N, Davies JR, Lessuileur T: Characterization of mucins produced by human HT29-MTX cell line. 5 h International workshop on Carcinoma Associated Mucins, Cambridge, LJK 1998.Google Scholar
  32. 32.2
    Swallow DM, Griffiths B, Bramwell ME, et al: Detection of the urinary “pum” polymorphism by the tumour binding monoclonal antibodies Cal, Ca2, HMFG-I and HMFG-2. Dis Markers 4:247–254, 1986.PubMedGoogle Scholar
  33. 33.2
    Takada A, Ohmori K, Yneda T, et al: Contribution of carbohydrate antigens sialyl Lewis a and sialyl Lewis x to adhesion of human cancer cells to vascular endothelium. Cancer Res. 53:354–361, 1993.PubMedGoogle Scholar
  34. 34.2
    Taylor-Papadimitriou J, Finn O: Biology, biochemistry and immunology of carcinoma associated mucins. Immunol Today 18:105–107, 1997.PubMedCrossRefGoogle Scholar
  35. 35.2
    Towbin H, Staehelin T, Gordon J: Electrophoretic transfer of proteins from polyacrilamide gels to nitrocellulose sheets: procedures and some applications. Proc Natl Acad Sci USA 76:4350–4354, 1979.PubMedCrossRefGoogle Scholar
  36. 36.2
    Vernham, GA, Crowther JA: Head and neck carcinoma: stage at presentation. Clin Otolaryngol 19:120–124, 1994.PubMedCrossRefGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2001

Authors and Affiliations

  • Maria V. Croce
    • 1
  • Martin E. Rabassa
    • 1
  • Mike R. Price
    • 2
  • Amada Segal-Eiras
    • 1
  1. 1.Centro de Investigaciones Inmunológicas Básicas y Aplicadas (CINIBA), Facultad de Ciencias MédicasUNLPLa PlataArgentina
  2. 2.School of Pharmaceutical SciencesUniversity of NottinghamUK

Personalised recommendations