Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1995 Oct;72(4):813–817. doi: 10.1038/bjc.1995.418

Evidence for mutual interdependence of epithelium and stromal lymphoid cells in a subset of papillary carcinomas.

M H Takahashi 1, G A Thomas 1, E D Williams 1
PMCID: PMC2034040  PMID: 7547225

Abstract

We have correlated the morphological features of 30 human thyroid carcinomas with the cellular localisation of insulin-like growth factor 1 (IGF-1) mRNA and IGF-1 receptor peptide using in situ hybridisation with digoxigenin-labelled oligoprobes and immunohistochemistry. Four of the five follicular carcinomas studied showed a consistent, uniform, strong positivity for IGF-1 mRNA in tumour cells compared with weakly positive surrounding normal follicular tissue and negative stroma. The majority of papillary carcinomas showed weak to moderate epithelial positivity for IGF-1 mRNA and negative stroma. Immunohistochemistry for IGF-1 receptor showed moderate positivity confined to the tumour epithelial cells in both follicular and the majority of papillary carcinomas. However, in a subgroup of papillary carcinomas characterised by a diffuse stromal lymphoid infiltration (n = 5), the stromal cells showed a much stronger reactivity for IGF-1 mRNA than the tumour or background thyroid, and the tumour cells showed a uniformly high level of immunoreactivity for IGF-1 receptor. These results are compatible with the growth of the papillary carcinoma in these cases being the result of a symbiotic relationship between the stromal lymphoid cells and the tumour epithelium with the lymphoid cells responding to an antigen produced by the tumour cells and the tumour cells responding to a growth factor produced by the lymphoid infiltrate. We suggest that this mechanism may be important in other tumours regularly associated with a widespread lymphoid infiltrate.

Full text

PDF
813

Images in this article

815Figure 1
on p.815
815Figure 2
on p.815

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bongarzone I., Pierotti M. A., Monzini N., Mondellini P., Manenti G., Donghi R., Pilotti S., Grieco M., Santoro M., Fusco A. High frequency of activation of tyrosine kinase oncogenes in human papillary thyroid carcinoma. Oncogene. 1989 Dec;4(12):1457–1462. [PubMed] [Google Scholar]
  2. Harach H. R., Escalante D. A., Onativia A., Lederer Outes J., Saravia Day E., Williams E. D. Thyroid carcinoma and thyroiditis in an endemic goitre region before and after iodine prophylaxis. Acta Endocrinol (Copenh) 1985 Jan;108(1):55–60. doi: 10.1530/acta.0.1080055. [DOI] [PubMed] [Google Scholar]
  3. Haugen D. R., Akslen L. A., Varhaug J. E., Lillehaug J. R. Demonstration of a TGF-alpha-EGF-receptor autocrine loop and c-myc protein over-expression in papillary thyroid carcinomas. Int J Cancer. 1993 Aug 19;55(1):37–43. doi: 10.1002/ijc.2910550108. [DOI] [PubMed] [Google Scholar]
  4. Hepler J. E., Van Wyk J. J., Lund P. K. Different half-lives of insulin-like growth factor I mRNAs that differ in length of 3' untranslated sequence. Endocrinology. 1990 Sep;127(3):1550–1552. doi: 10.1210/endo-127-3-1550. [DOI] [PubMed] [Google Scholar]
  5. Jass J. R., Atkin W. S., Cuzick J., Bussey H. J., Morson B. C., Northover J. M., Todd I. P. The grading of rectal cancer: historical perspectives and a multivariate analysis of 447 cases. Histopathology. 1986 May;10(5):437–459. doi: 10.1111/j.1365-2559.1986.tb02497.x. [DOI] [PubMed] [Google Scholar]
  6. Khan G., Coates P. J., Kangro H. O., Slavin G. Epstein Barr virus (EBV) encoded small RNAs: targets for detection by in situ hybridisation with oligonucleotide probes. J Clin Pathol. 1992 Jul;45(7):616–620. doi: 10.1136/jcp.45.7.616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lemoine N. R., Mayall E. S., Wyllie F. S., Williams E. D., Goyns M., Stringer B., Wynford-Thomas D. High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis. Oncogene. 1989 Feb;4(2):159–164. [PubMed] [Google Scholar]
  8. Neonakis E., Thomas G. A., Davies H. G., Wheeler M. H., Williams E. D. Expression of calcitonin and somatostatin peptide and mRNA in medullary thyroid carcinoma. World J Surg. 1994 Jul-Aug;18(4):588–593. doi: 10.1007/BF00353772. [DOI] [PubMed] [Google Scholar]
  9. Ollis C. A., Hill D. J., Munro D. S. A role for insulin-like growth factor-I in the regulation of human thyroid cell growth by thyrotrophin. J Endocrinol. 1989 Dec;123(3):495–500. doi: 10.1677/joe.0.1230495. [DOI] [PubMed] [Google Scholar]
  10. Onoda N., Ohmura E., Tsushima T., Ohba Y., Emoto N., Isozaki O., Sato Y., Shizume K., Demura H. Autocrine role of insulin-like growth factor (IGF)-I in a human thyroid cancer cell line. Eur J Cancer. 1992;28A(11):1904–1909. doi: 10.1016/0959-8049(92)90033-x. [DOI] [PubMed] [Google Scholar]
  11. Phillips I. D., Becks G. P., Logan A., Wang J. F., Smith C., Hill D. J. Altered expression of insulin-like growth factor-I (IGF-I) and IGF binding proteins during rat thyroid hyperplasia and involution. Growth Factors. 1994;10(3):207–222. doi: 10.3109/08977199409000239. [DOI] [PubMed] [Google Scholar]
  12. Soos M. A., Field C. E., Lammers R., Ullrich A., Zhang B., Roth R. A., Andersen A. S., Kjeldsen T., Siddle K. A panel of monoclonal antibodies for the type I insulin-like growth factor receptor. Epitope mapping, effects on ligand binding, and biological activity. J Biol Chem. 1992 Jun 25;267(18):12955–12963. [PubMed] [Google Scholar]
  13. Thomas G. A., Davies H. G., Williams E. D. Demonstration of mRNA using digoxigenin labelled oligonucleotide probes for in situ hybridisation in formamide free conditions. J Clin Pathol. 1993 Feb;46(2):171–174. doi: 10.1136/jcp.46.2.171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Thomas G. A., Davies H. G., Williams E. D. Site of production of IGF1 in the normal and stimulated mouse thyroid. J Pathol. 1994 Aug;173(4):355–360. doi: 10.1002/path.1711730411. [DOI] [PubMed] [Google Scholar]
  15. Werther G. A., Hintz R. L., Rosenfeld R. G. Up-regulation of IGF-I receptors on IM-9 cells by IGF-II peptides. Horm Metab Res. 1989 Mar;21(3):109–112. doi: 10.1055/s-2007-1009166. [DOI] [PubMed] [Google Scholar]
  16. Williams D. W., Williams E. D., Wynford-Thomas D. Evidence for autocrine production of IGF-1 in human thyroid adenomas. Mol Cell Endocrinol. 1989 Jan;61(1):139–143. doi: 10.1016/0303-7207(89)90199-8. [DOI] [PubMed] [Google Scholar]
  17. Williams D. W., Williams E. D., Wynford-Thomas D. Loss of dependence on IGF-1 for proliferation of human thyroid adenoma cells. Br J Cancer. 1988 Jun;57(6):535–539. doi: 10.1038/bjc.1988.124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Williams D. W., Wynford-Thomas D., Williams E. D. Control of human thyroid follicular cell proliferation in suspension and monolayer culture. Mol Cell Endocrinol. 1987 May;51(1-2):33–40. doi: 10.1016/0303-7207(87)90116-x. [DOI] [PubMed] [Google Scholar]
  19. Yee D., Paik S., Lebovic G. S., Marcus R. R., Favoni R. E., Cullen K. J., Lippman M. E., Rosen N. Analysis of insulin-like growth factor I gene expression in malignancy: evidence for a paracrine role in human breast cancer. Mol Endocrinol. 1989 Mar;3(3):509–517. doi: 10.1210/mend-3-3-509. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES