Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2000 May 18;82(12):1958–1966. doi: 10.1054/bjoc.2000.1162

Immunocytochemical assessment of sigma-1 receptor and human sterol isomerase in breast cancer and their relationship with a series of prognostic factors

J Simony-Lafontaine 1, M Esslimani 1, E Bribes 4, S Gourgou 2, N Lequeux 1, R Lavail 1, J Grenier 3, A Kramar 2, P Casellas 4
PMCID: PMC2363255  PMID: 10864204

Abstract

The purpose of this study was to immunocytochemically investigate two new markers, the sigma-1 receptor and the human sterol isomerase (hSI), in comparison with a series of clinicopathological and immunocytochemical prognostic factors in a trial including 95 patients with operable primary breast cancers. Our results showed no statistically significant relationship between these two markers and the age of the patients, their menopausal status, the tumour size and its histological grade, the nodal status and the expression of the Ki-67 proliferative marker. However, we evidenced a close correlation between the sigma-1 receptor expression and the hormonal receptor positivity (P = 0.008), essentially due to a link with the progesterone receptor status (P = 0.01). By contrast there was an inverse relationship between hSI expression and the oestrogen receptor and/or progesterone receptor positivity (P = 0.098). A significant relationship was shown between both the sigma-1 receptor, hSI expressions and Bcl2 expression, with P = 0.017 and 0.035 respectively. We also assessed whether the expression of the sigma-1 receptor or hSI might be linked with disease-free survival (DFS) and found that the presence of hSI and the absence of sigma-1 receptor expression were associated with a poorer disease-free survival (P = 0.007). Altogether these results suggest that in primary breast carcinomas in association with the evaluation of the steroid receptor status, the sigma-1 receptor and hSI may be interesting new markers useful to identify those patients who might be able to benefit from an adjuvant therapy. © 2000 Cancer Research Campaign

Keywords: sigma-1 receptor, human sterol isomerase, SR-BP-1, immunocytochemistry, breast cancer, prognostic factors

Full Text

The Full Text of this article is available as a PDF (748.2 KB).

Selected References

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

  1. BLOOM H. J., RICHARDSON W. W. Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer. 1957 Sep;11(3):359–377. doi: 10.1038/bjc.1957.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bukholm I. K., Nesland J. M., Kåresen R., Jacobsen U., Børresen-Dale A. L. Interaction between bcl-2 and p21 (WAF1/CIP1) in breast carcinomas with wild-type p53. Int J Cancer. 1997 Sep 26;73(1):38–41. doi: 10.1002/(sici)1097-0215(19970926)73:1<38::aid-ijc7>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  3. Casellas P., Bourrié B., Canat X., Carayon P., Buisson I., Paul R., Brelière J. C., Le Fur G. Immunopharmacological profile of SR 31747: in vitro and in vivo studies on humoral and cellular responses. J Neuroimmunol. 1994 Jul;52(2):193–203. doi: 10.1016/0165-5728(94)90113-9. [DOI] [PubMed] [Google Scholar]
  4. Collett K., Hartveit F., Skjaerven R., Maehle B. O. Prognostic role of oestrogen and progesterone receptors in patients with breast cancer: relation to age and lymph node status. J Clin Pathol. 1996 Nov;49(11):920–925. doi: 10.1136/jcp.49.11.920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Derocq J. M., Bourrié B., Ségui M., Le Fur G., Casellas P. In vivo inhibition of endotoxin-induced pro-inflammatory cytokines production by the sigma ligand SR 31747. J Pharmacol Exp Ther. 1995 Jan;272(1):224–230. [PubMed] [Google Scholar]
  6. Dussossoy D., Carayon P., Belugou S., Feraut D., Bord A., Goubet C., Roque C., Vidal H., Combes T., Loison G. Colocalization of sterol isomerase and sigma(1) receptor at endoplasmic reticulum and nuclear envelope level. Eur J Biochem. 1999 Jul;263(2):377–386. doi: 10.1046/j.1432-1327.1999.00500.x. [DOI] [PubMed] [Google Scholar]
  7. Elston C. W., Ellis I. O. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991 Nov;19(5):403–410. doi: 10.1111/j.1365-2559.1991.tb00229.x. [DOI] [PubMed] [Google Scholar]
  8. Gee J. M., Robertson J. F., Ellis I. O., Willsher P., McClelland R. A., Hoyle H. B., Kyme S. R., Finlay P., Blamey R. W., Nicholson R. I. Immunocytochemical localization of BCL-2 protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy. Int J Cancer. 1994 Dec 1;59(5):619–628. doi: 10.1002/ijc.2910590508. [DOI] [PubMed] [Google Scholar]
  9. Hawkins R. A., Tesdale A. L., Killen M. E., Jack W. J., Chetty U., Dixon J. M., Hulme M. J., Prescott R. J., McIntyre M. A., Miller W. R. Prospective evaluation of prognostic factors in operable breast cancer. Br J Cancer. 1996 Nov;74(9):1469–1478. doi: 10.1038/bjc.1996.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hellemans P., van Dam P. A., Weyler J., van Oosterom A. T., Buytaert P., Van Marck E. Prognostic value of bcl-2 expression in invasive breast cancer. Br J Cancer. 1995 Aug;72(2):354–360. doi: 10.1038/bjc.1995.338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hockenbery D., Nuñez G., Milliman C., Schreiber R. D., Korsmeyer S. J. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990 Nov 22;348(6299):334–336. doi: 10.1038/348334a0. [DOI] [PubMed] [Google Scholar]
  12. Jbilo O., Vidal H., Paul R., De Nys N., Bensaid M., Silve S., Carayon P., Davi D., Galiègue S., Bourrié B. Purification and characterization of the human SR 31747A-binding protein. A nuclear membrane protein related to yeast sterol isomerase. J Biol Chem. 1997 Oct 24;272(43):27107–27115. doi: 10.1074/jbc.272.43.27107. [DOI] [PubMed] [Google Scholar]
  13. Johnston S. R., MacLennan K. A., Sacks N. P., Salter J., Smith I. E., Dowsett M. Modulation of Bcl-2 and Ki-67 expression in oestrogen receptor-positive human breast cancer by tamoxifen. Eur J Cancer. 1994;30A(11):1663–1669. doi: 10.1016/0959-8049(94)00327-2. [DOI] [PubMed] [Google Scholar]
  14. Korsmeyer S. J. Bcl-2 initiates a new category of oncogenes: regulators of cell death. Blood. 1992 Aug 15;80(4):879–886. [PubMed] [Google Scholar]
  15. Labit-Le Bouteiller C., Jamme M. F., David M., Silve S., Lanau C., Dhers C., Picard C., Rahier A., Taton M., Loison G. Antiproliferative effects of SR31747A in animal cell lines are mediated by inhibition of cholesterol biosynthesis at the sterol isomerase step. Eur J Biochem. 1998 Sep 1;256(2):342–349. doi: 10.1046/j.1432-1327.1998.2560342.x. [DOI] [PubMed] [Google Scholar]
  16. Leek R. D., Kaklamanis L., Pezzella F., Gatter K. C., Harris A. L. bcl-2 in normal human breast and carcinoma, association with oestrogen receptor-positive, epidermal growth factor receptor-negative tumours and in situ cancer. Br J Cancer. 1994 Jan;69(1):135–139. doi: 10.1038/bjc.1994.22. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mink D., von Tongelen B., Villena-Heinsen C., Heiss C., Schmidt W. Breast cancer and prognostic factors. Tumour size, degree of differentiation, proliferation kinetics and expression of steroid hormone receptors. Eur J Gynaecol Oncol. 1994;15(6):424–436. [PubMed] [Google Scholar]
  18. Paul R., Silve S., De Nys N., Dupuy P. H., Bouteiller C. L., Rosenfeld J., Ferrara P., Le Fur G., Casellas P., Loison G. Both the immunosuppressant SR31747 and the antiestrogen tamoxifen bind to an emopamil-insensitive site of mammalian Delta8-Delta7 sterol isomerase. J Pharmacol Exp Ther. 1998 Jun;285(3):1296–1302. [PubMed] [Google Scholar]
  19. Pichon M. F., Broet P., Magdelenat H., Delarue J. C., Spyratos F., Basuyau J. P., Saez S., Rallet A., Courriere P., Millon R. Prognostic value of steroid receptors after long-term follow-up of 2257 operable breast cancers. Br J Cancer. 1996 Jun;73(12):1545–1551. doi: 10.1038/bjc.1996.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Robertson J. F. Oestrogen receptor: a stable phenotype in breast cancer. Br J Cancer. 1996 Jan;73(1):5–12. doi: 10.1038/bjc.1996.2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Seth P., Leibach F. H., Ganapathy V. Cloning and structural analysis of the cDNA and the gene encoding the murine type 1 sigma receptor. Biochem Biophys Res Commun. 1997 Dec 18;241(2):535–540. doi: 10.1006/bbrc.1997.7840. [DOI] [PubMed] [Google Scholar]
  22. Silve S., Leplatois P., Josse A., Dupuy P. H., Lanau C., Kaghad M., Dhers C., Picard C., Rahier A., Taton M. The immunosuppressant SR 31747 blocks cell proliferation by inhibiting a steroid isomerase in Saccharomyces cerevisiae. Mol Cell Biol. 1996 Jun;16(6):2719–2727. doi: 10.1128/mcb.16.6.2719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Su T. P. Sigma receptors. Putative links between nervous, endocrine and immune systems. Eur J Biochem. 1991 Sep 15;200(3):633–642. doi: 10.1111/j.1432-1033.1991.tb16226.x. [DOI] [PubMed] [Google Scholar]
  24. van Slooten H. J., van de Vijver M. J., van de Velde C. J., van Dierendonck J. H. Loss of Bcl-2 in invasive breast cancer is associated with high rates of cell death, but also with increased proliferative activity. Br J Cancer. 1998 Mar;77(5):789–796. doi: 10.1038/bjc.1998.128. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES