Skip to main content

Advertisement

Log in

A basal membrane-like structure surrounding tumour nodules may prevent intraepithelial leucocyte infiltration in colorectal cancer

  • Original Article
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Epithelial tumours consist of an epithelial compartment and a stromal compartment, which are sometimes separated by a basal membrane-like structure. We sought to determine whether these factors have prognostic value in 84 curatively resected stage II and III colorectal cancer by immunohistochemically staining tumours for leucocytes (CD45) and extracellular matrix, and to assess the presence of a basal membrane-like structure. Leucocyte infiltration was also assessed in hematoxylin-eosin (HE) stained sections. Most leucocytes were located in the tumour stroma. A relatively high intraepithelial leucocyte infiltration was significantly correlated with a lower level of tumour recurrence (P=0.03) and a longer disease-free survival (P=0.05), whereas leucocytes located in the tumour stroma (P=0.92) or at the advancing margin (p=0.06) were not. Intraepithelial leucocyte infiltration was also significantly correlated with leucocyte infiltration in the tumour stroma (P=0.02) and at the advancing tumour margin (P=0.005), and as assessed in HE-stained tumour sections (P=0.05), but each of these parameters on its own did not have a prognostic value in predicting disease-free survival. Moreover, the presence of a basal membrane-like structure surrounding the tumour epithelium was inversely correlated with the number of intraepithelial leucocytes (P=0.05), suggesting that this membrane-like structure functions as a barrier to intraepithelial leucocyte infiltration. We conclude that leucocytes must be in the direct vicinity of tumour cells to affect tumour growth. The presence of an extracellular matrix barrier seems to prevent this interaction.

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.

Fig. 1. A
Fig. 2.

Similar content being viewed by others

References

  1. Coca S, Perez PJ, Martinez D, Colmenarejo A, Saez MA, Vallejo C, Martos JA, Moreno M (1997) The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma. Cancer 79:2320–2328

    Article  CAS  PubMed  Google Scholar 

  2. Diederichsen AC, Zeuthen J, Christensen PB, Kristensen T (1999) Characterisation of tumour infiltrating lymphocytes and correlations with immunological surface molecules in colorectal cancer. Eur J Cancer 35:721–726

    Article  CAS  PubMed  Google Scholar 

  3. Dolcetti R, Viel A, Doglioni C, Russo A, Guidoboni M, Capozzi E, Vecchiato N, Macri E, Fornasarig M, Boiocchi M (1999) High prevalence of activated intraepithelial cytotoxic T lymphocytes and increased neoplastic cell apoptosis in colorectal carcinomas with microsatellite instability. Am J Pathol 154:1805–1813

    CAS  PubMed  Google Scholar 

  4. Greenlee RT, Murray T, Bolden S, Wingo PA (2000) Cancer statistics, 2000. CA Cancer J Clin 50:7–33

    CAS  PubMed  Google Scholar 

  5. Hagenaars M, Ensink NG, Basse PH, Hokland M, Nannmark U, Eggermont AM, van de Velde CJ, Fleuren GJ, Kuppen PJ (2000) The microscopic anatomy of experimental rat CC531 colon tumour metastases: consequences for immunotherapy? Clin Exp Metastasis 18:189–196

    Article  CAS  PubMed  Google Scholar 

  6. Hewitt RE, Powe DG, Griffin NR, Turner DR (1991) Relationships between epithelial basement membrane staining patterns in primary colorectal carcinomas and the extent of tumour spread. Int J Cancer 48:855–860

    CAS  PubMed  Google Scholar 

  7. Jackson PA, Green MA, Marks CG, King RJ, Hubbard R, Cook MG (1996) Lymphocyte subset infiltration patterns and HLA antigen status in colorectal carcinomas and adenomas. Gut 38:85–89

    CAS  PubMed  Google Scholar 

  8. Jass JR, Love SB, Northover JM (1987) A new prognostic classification of rectal cancer. Lancet 1:1303–1306

    CAS  PubMed  Google Scholar 

  9. Jonges LE, Nagelkerke JF, Ensink NG, van der Velde EA, Tollenaar RA, Fleuren GJ, van de Velde CJ, Morreau H, Kuppen PJ (2001) Caspase-3 activity as a prognostic factor in colorectal carcinoma. Lab Invest 81:681–688

    CAS  PubMed  Google Scholar 

  10. Kerr DJ, Midgley RS (2000) Immunotherapy for colorectal cancer: potential application in an adjuvant setting. Semin Oncol 27:132–137

    CAS  PubMed  Google Scholar 

  11. Kirchner T, Brabletz T (2000) Patterning and nuclear beta-catenin expression in the colonic adenoma-carcinoma sequence. Analogies with embryonic gastrulation. Am J Pathol 157:1113–1121

    CAS  PubMed  Google Scholar 

  12. Kuppen PJ, van der Eb MM, Jonges LE, Hagenaars M, Hokland ME, Nannmark U, Goldfarb RH, Basse PH, Fleuren GJ, Hoeben RC, van de Velde CJ (2001) Tumor structure and extracellular matrix as a possible barrier for therapeutic approaches using immune cells or adenoviruses in colorectal cancer. Histochem Cell Biol 115:67–72

    CAS  PubMed  Google Scholar 

  13. Lohi J, Oivula J, Kivilaakso E, Kiviluoto T, Frojdman K, Yamada Y, Burgeson RE, Leivo I, Virtanen I (2000) Basement membrane laminin-5 is deposited in colorectal adenomas and carcinomas and serves as a ligand for alpha3beta1 integrin. APMIS 108:161–172

    CAS  PubMed  Google Scholar 

  14. Mahida YR, Galvin AM, Gray T, Makh S, McAlindon ME, Sewell HF, Podolsky DK (1997) Migration of human intestinal lamina propria lymphocytes, macrophages and eosinophils following the loss of surface epithelial cells. Clin Exp Immunol 109:377–386

    CAS  PubMed  Google Scholar 

  15. Martinez HA (1988) The extracellular matrix and neoplasia. Lab Invest 58:609–612

    PubMed  Google Scholar 

  16. McAlindon ME, Gray T, Galvin A, Sewell HF, Podolsky DK, Mahida YR (1998) Differential lamina propria cell migration via basement membrane pores of inflammatory bowel disease mucosa. Gastroenterology 115:841–848

    CAS  PubMed  Google Scholar 

  17. Mukai S, Kjaergaard J, Shu S, Plautz GE (1999) Infiltration of tumors by systemically transferred tumor-reactive T lymphocytes is required for antitumor efficacy. Cancer Res 59:5245–5249

    CAS  PubMed  Google Scholar 

  18. Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H, Ohtani H (1998) CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 58:3491–3494

    CAS  PubMed  Google Scholar 

  19. O'Connell J, Bennett MW, O'Sullivan GC, Roche D, Kelly J, Collins JK, Shanahan F (1998) Fas ligand expression in primary colon adenocarcinomas: evidence that the Fas counterattack is a prevalent mechanism of immune evasion in human colon cancer. J Pathol 186:240–246

    CAS  PubMed  Google Scholar 

  20. Ostenstad B, Lea T, Schlichting E, Harboe M (1994) Human colorectal tumour infiltrating lymphocytes express activation markers and the CD45RO molecule, showing a primed population of lymphocytes in the tumour area. Gut 35:382–387

    CAS  PubMed  Google Scholar 

  21. Risio M, Reato G, di Celle PF, Fizzotti M, Rossini FP, Foa R (1996) Microsatellite instability is associated with the histological features of the tumor in nonfamilial colorectal cancer. Cancer Res 56:5470–5474

    CAS  PubMed  Google Scholar 

  22. Robson H, Anderson E, James RD, Schofield PF (1996) Transforming growth factor beta 1 expression in human colorectal tumours: an independent prognostic marker in a subgroup of poor prognosis patients. Br J Cancer 74:753–758

    CAS  PubMed  Google Scholar 

  23. Svennevig JL, Lunde OC, Holter J, Bjorgsvik D (1984) Lymphoid infiltration and prognosis in colorectal carcinoma. Br J Cancer 49:375–377

    CAS  PubMed  Google Scholar 

  24. Tollenaar RA, van Krieken JH, van Slooten HJ, Bruinvels DJ, Nelemans KM, van den Broek LJ, Hermans J, van Dierendonck JH (1998) Immunohistochemical detection of p53 and Bcl-2 in colorectal carcinoma: no evidence for prognostic significance. Br J Cancer 77:1842–1847

    CAS  PubMed  Google Scholar 

  25. Tsushima H, Kawata S, Tamura S, Ito N, Shirai Y, Kiso S, Imai Y, Shimomukai H, Nomura Y, Matsuda Y, Matsuzawa Y (1996) High levels of transforming growth factor beta 1 in patients with colorectal cancer: association with disease progression. Gastroenterology 110:375–382

    CAS  PubMed  Google Scholar 

  26. Wojtowicz-Praga S (1997) Reversal of tumor-induced immunosuppression: a new approach to cancer therapy. J Immunother 20:165–177

    CAS  PubMed  Google Scholar 

  27. Yip D, Strickland AH, Karapetis CS, Hawkins CA, Harper PG (2000) Immunomodulation therapy in colorectal carcinoma. Cancer Treat Rev 26:169–190

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Dr. A. Gorter for helpful discussions and we would also like to acknowledge the assistance of Mr. K. van der Ham with the preparation of the photographs of tissue slides.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter J. K. Kuppen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Menon, A.G., Fleuren, G.J., Alphenaar, E.A. et al. A basal membrane-like structure surrounding tumour nodules may prevent intraepithelial leucocyte infiltration in colorectal cancer. Cancer Immunol Immunother 52, 121–126 (2003). https://doi.org/10.1007/s00262-002-0363-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-002-0363-6

Keywords

Navigation