Skip to main content
Log in

Correlative histochemical study providing evidence for the dual nature of human colorectal cancer mucin

  • Published:
The Histochemical Journal Aims and scope Submit manuscript

Summary

Luminal secretions within colorectal cancers have been assumed to be the counterpart of normal goblet cell mucin. The aim of this study was to establish whether secretory material within colorectal cancers may in fact be traced to different lineages: goblet cells and columnar cells. The distribution of the apomucins MUC1 and MUC2, non-O-acetylated sialic acid and the carbohydrate structures sialosyl Tn, Tn, Lewisx, sialosyl Lewisx and Lewisy was studied in normal colorectal mucosa and colorectal cancer specimens using standard histochemical techniques. Unmasking of MUC1 and MUC2 was achieved using periodic acid and saponification-neuraminidase-periodic acid pretreatment respectively. Within normal and malignant epithelium, correlations and/or co-localization could be demonstrated for goblet cells with MUC2, non-O-acetylated sialic acid, sialosyl Tn, Tn (Golgi region) and sialosyl Lewisx, and for columnar cells with MUC1, Lewisx, sialosyl Lex, Tn (cytoplasm) and Lewisy (UEA-1). The goblet cell spectrum was associated with mucin-like (type I) luminal secretions within cancers, whereas the columnar cell spectrum characterized non-mucin-like (type II) secretions and intracytoplasmic lumina. These data indicate that colorectal cancer mucin can be broadly separated into two types: secretory mucin linked to cells of goblet lineage and up-regulated membrane-associated mucin of presumed columnar cell origin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ajioka, Y., Allison, L.J. & Jass, J.R. (1996) Significance of MUC1 and MUC2 mucin expression in colorectal cancer. J. Clin. Pathol. 49, 560-4.

    Article  PubMed  CAS  Google Scholar 

  • Battifora, H. (1975) Intracytoplasmic lumina in breast carcinoma. Arch. Pathol. 99, 614-17.

    PubMed  CAS  Google Scholar 

  • Chang, S-K., Dohrman, A.F., Basbaum, C.B., Ho, S.B., Tsuda, T., Toribara, N.W., Gum, J.R. & Kim, Y.S. (1994) Localization of Mucin (MUC2 and MUC3) messenger RNA and peptide expression in human normal intestine and colon cancer. Gastroenterology 107, 28-39.

    PubMed  CAS  Google Scholar 

  • Corcoran, D., Walker, R.A., Barley, J. & Ojakian, G.K. (1990) Ultrastructural localization of milk fat globule membrane antigens in human breast carcinomas. J. Pathol. 161, 161-6.

    Article  PubMed  CAS  Google Scholar 

  • Davidson, S.E., Mckenzie, J.L., Beard, M.E.J. & Hart, D.N.J. (1988) The tissue distribution of the 3·-fucosyl-N-acetyl lactosamine determinant recognized by the CD15 monoclonal antibodies CMRF-7 and 27. Pathology 20, 24-31.

    Article  PubMed  CAS  Google Scholar 

  • Eusebi, V., Pich, A., Macchiorlatti, E. & Bussolati, G. (1977) Morpho-functional differentiation in lobular carcinoma of the breast. Histopathology 1, 307-14.

    Article  Google Scholar 

  • Fuller, C.E., Davies, R.P., Williams, G.T. & Williams, E.D. (1990) Crypt restricted heterogeneity of goblet cell mucus glycoprotein in histologically normal human colonic mucosa: a potential marker of somatic mutation. Br. J. Cancer 61, 382-4.

    PubMed  CAS  Google Scholar 

  • Gendler, S.J., Lancaster, C.A., Taylor-Papadimitriou, J., Duhig, T., Peat, N., Burchell, J., Pemberton, L., Lalani, E-N. & Wilson, D. (1990) Molecular cloning and expression of a human tumor-associated polymorphic epithelial mucin. J. Biol. Chem. 265, 15286-93.

    PubMed  CAS  Google Scholar 

  • Gendler, S.J., Spicer, A.P., Lalani, E.N., Duhig, T., Peat, N., Burchell, J., Pemberton, L., Boshell, M. & Taylor-Papadimitriou, J. (1991) Structure and biology of a carcinoma-associated mucin, MUC1. Am. Rev. Respir. Dis. 144, S42-7.

    PubMed  CAS  Google Scholar 

  • Ghadially, F.N. (1988) Cytoplasmic matrix and its inclusions. Intracytoplasmic canaliculi and lumina. In Ultrastructural Pathology of the Cell and Matrix, Vol II, 3rd edn. pp. 1010-18. London: Butterworths.

    Google Scholar 

  • Hanski, C., Drechsler, K., Hanisch, F-G., Sheehan, J., Manske, M., Ogorek, D., Klussmann, E., Hanski, M-L., Blank, M., Xing, P-X., Mckenzie, I.F.C., Devine, P.L. Riecken, E-O. (1993) Altered glycosylation of the MUC-1 protein core contributes to the colon carcinoma-associated increase of mucin-bound sialyl-Lewisx expression. Cancer Res. 53, 4082-8.

    PubMed  CAS  Google Scholar 

  • Hanski, C., Hanski, M-L., Zimmer, T., Ogorek, D., Devine, P. & Riecken, E-O. (1995) Characterization of the major sialyl-Lex-positive mucin present in colon, colon carcinoma, and sera of patients with colorectal cancer. Cancer Res. 55, 928-33.

    PubMed  CAS  Google Scholar 

  • Hindsgaul, O., Norberg, T., Le Pendu, J. & Lemieux, R.U. (1982) Synthesis of type 2 human blood-group antigenic determinants. The H, X and Y haptens and variations of the H type 2 determinant as probes for the combining site of the lectin 1 of Ulex europaeus. Carbohydr. Res. 109, 109-42.

    Article  PubMed  CAS  Google Scholar 

  • Hinoda, Y., Nakagawa, N., Ohe, Y., Kakiuchi, H., Tsujisaki, M., Imai, K. & Yachi, A. (1990) Recognition of the polypeptide core of mucin by monoclonal antibody MUSE11 against an adenocarcinoma-associated antigen. Jpn. J. Cancer Res. 81, 1206-9.

    PubMed  CAS  Google Scholar 

  • Jass, J.R. & Roberton, A.M. (1994) Colorectal mucin histochemistry in health and disease: a critical review. Pathol. Int. 44, 487-504.

    Article  PubMed  CAS  Google Scholar 

  • Jass, J.R. & Smith, M. (1992) Sialic acid and epithelial differentiation in colorectal polyp and cancer — a morphological, mucin and lectin histochemical study. Pathology 24, 233-42.

    Article  PubMed  CAS  Google Scholar 

  • Jass, J.R. & Sobin, L.H. (eds) (1989) Histological Typing of Intestinal Tumors (WHO), 2nd edn. Berlin: Springer-Verlag.

    Google Scholar 

  • Jass, J.R., Allison, L.M. & Edgar, S. (1994) Monoclonal antibody TKH2 to the cancer-associated epitope sialosyl Tn shows cross-reactivity with variants of normal colorectal goblet cell mucin. Pathology 26, 418-22.

    Article  PubMed  CAS  Google Scholar 

  • Jass, J.R., Allison, L.J. & Edgar, S.D. (1995) Distribution of sialosyl Tn and Tn antigens within normal and malignant colorectal epithelium. J. Pathol. 176, 143-9.

    Article  PubMed  CAS  Google Scholar 

  • Nesland, J.M., Holm, R. & Johannessen, J.V. (1985) Ultrastructural and immunohistochemical features of lobular carcinoma of the breast. J. Pathol. 145, 39-52.

    Article  PubMed  CAS  Google Scholar 

  • O'Donnell, M. & Al-Nafussi, A.I. (1995) Intracytoplasmic lumina and mucinous inclusions in ovarian carcinomas. Histopathology 26, 181-4.

    Article  PubMed  Google Scholar 

  • Ogata, S., Uehara, H., Chen, A. & Itzkowitz, S.H. (1992) Mucin gene expression in colonic tissues and cell lines. Cancer Res. 52, 5971-8.

    PubMed  CAS  Google Scholar 

  • Ogata, S., Ho, I., Chen, A., Dubois, D., Maklansky, J., Singhal, A., Hakomori, S. & Itzkowitz, S. (1995) Tumor-associated sialylated antigens are constitutively expressed in normal human colonic mucosa. Cancer Res. 55, 1869-74.

    PubMed  CAS  Google Scholar 

  • Quincey, C., Raitt, N., Bell, J. & Ellis, I.O. (1991) Intracytoplasmic lumina-a useful diagnostic feature of adenocarcinoma. Histopathology 19, 83-7.

    Article  PubMed  CAS  Google Scholar 

  • Sugihara, K. & Jass, J.R. (1986) Colorectal goblet cell sialomucin heterogeneity: its relation to malignant disease. J. Clin. Pathol. 39, 1088-95.

    Article  PubMed  CAS  Google Scholar 

  • Tytgat, K.M.A.J., BÜller, H.A., Opdam, F.J.M., Kim, Y.S., Einerhand, A.W.C. & Dekker, J. (1994) Biosynthesis of human colonic mucin: MUC2 is the prominent secretory mucin. Gastroenterology 107, 1352-63.

    PubMed  CAS  Google Scholar 

  • Veh, R.W., Meesen, D., Kuntz, D. & May, B. (1982) Histochemical demonstration of side-chain substituted sialic acid. In Colonic Carcinogenesis (edited by Malt, R.A. & Williamson, R.C.N.) pp. 355-65. Lancaster: MTP Press.

    Google Scholar 

  • Xing, P.X., Prenzoska, J., Layton, G.T., Devine, P.L. & Mckenzie, I.F.C. (1992) Second generation monoclonal antibodies to intestinal MUC2 peptide reactive with colon cancer. J. Natl. Cancer. Inst. 84, 699-703.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ajioka, Y., Xing, PX., Hinoda, Y. et al. Correlative histochemical study providing evidence for the dual nature of human colorectal cancer mucin. J Mol Hist 29, 143–152 (1997). https://doi.org/10.1023/A:1026485306044

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026485306044

Keywords

Navigation