Skip to main content
SpringerLink
Log in

The relationship of cytoplasmic intermediate filaments and membrane antigens with hormone receptors, nuclear staining density, and mode of stromal invasion in human breast cancer

  • Report
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Serial sections on biopsies of 26 women with invasive breast carcinoma were stained for low molecular weight keratins (LKER), high molecular weight keratins (HKER), epithelial membrane antigen (EMA), vimentin (VIM), carcinoembryonic antigen (mCEA and pCEA), and nuclear estrogen (mER) and progesterone receptors (mPGR), using monoclonal and polyclonal sera. Specified areas were identified on serially sectioned slides and staining reactions were compared among areas as well as among patients.

The study concludes: (1) LKER staining was positively related to (a) the percentage of tumor cells with densely stained nuclei, (b) a trabecular mode of stromal invasion, and (c) HKER and EMA staining, and inversely related to (d) VIM staining and gross tumor size. (2) HKER was also inversely related to gross tumor size. (3) VIM staining was positively related to pCEA staining. (4) VIM staining was inversely related to staining ER and PGR. (5) LKER, HKER, and EMA staining was stronger in areas of trabecular rather than confluent areas of stromal invasion within the same biopsy. (6) Staining for ER and PGR was not related to mode of stromal invasion, but showed a strong inverse relationship with mitotic index.

Positive staining for LKER may be an indicator of better differentiation together with densely staining nuclei and trabecular mode of stromal invasion, whilst VIM and pCEA appear to be related to features indicative of lack of differentiation. Hormone receptor positivity seems to be strongly related to mitotic activity rather than differentiation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Bell CD, Shokry PE, Stadler J: The relationship of nuclear staining density and mode of stromal invasion with axillary metastases and hormone receptor status in human breast cancer. Am J Clin Pathol 91: 377–385, 1989

    Google Scholar 

  2. Caspersson T, Santesson L: Studies on protein metabolism in the cells of epithelial tumors. Acta Radiol Suppl (Stockh) 46: 1–105, 1942

    Google Scholar 

  3. Antoniades K, Spector H: Correlation of estrogen receptor levels with histology and cytomorphology in human mammary cancer. Am J Clin Pathol 71: 497–503, 1979

    Google Scholar 

  4. McCarty KS Jr, Barton TK, Fetter BF, Woodard BH, Mossler JA, Reeves W, Daly J, Wilkinson WE, McCarty KS Sr: Correlation of estrogen and progesterone receptors with histological differentiation in mammary carcinoma. Cancer 46: 2851–2858, 1980

    Google Scholar 

  5. Visscher DW, Zarbo RJ, Jacobsen G, Kambouris A, Talpos G, Sakr W, Crissman JD: Multiparametric deoxyribonucleic acid and cell cycle analysis of breast carcinomas by flow cytometry. Clinicopathologic correlations. Lab Invest 62: 370–378, 1990

    Google Scholar 

  6. Scarff RW, Torloni H: Histological typing of breast tumors. International Histological Classification of Tumors, no. 14. Geneva: World Health Organization 19–20, 1968

    Google Scholar 

  7. McGuire WL, De la Garza M: Improved sensitivity in the measurement of estrogen receptors in human breast cancer. J Clin Endocrinol Metab 37: 986–989, 1973

    Google Scholar 

  8. McGuire WL, Horwitz KB, Pearson OH, Segaloff A: Current status of estrogen and progesterone receptors in breast cancer. Cancer 39: 2934–2947, 1977

    Google Scholar 

  9. Black MM, Speer FD: Nuclear structure in cancer tissues. Surg Gynecol Obstet 105: 97–102, 1957

    Google Scholar 

  10. Cutler SJ, Black MM, Friedell GH, Vidone RA, Goldenberg IS: Prognostic factors in cancer of the female breast. II. Reproducibility of histopathological classification. Cancer 19: 75–82, 1966

    Google Scholar 

  11. Pinkus GS, Kurtin PJ: Epithelial membrane antigen - a diagnostic discriminant in surgical pathology: immunohistochemical profile in epithelial, mesenchymal, and hematopoietic neoplasms using paraffin sections and monoclonal antibodies. Hum Pathol 16: 929–940, 1985

    Google Scholar 

  12. Snedecor GW: Statistical Methods, 5th ed. The Iowa State University Press, Ames, Iowa, 282–285, 1966

    Google Scholar 

  13. Baildam AD, Howell A, Barnes DM, Turnbull L, Sellwood RA: The expression of milk fat globule antigens within human mammary tumours: the relationship to steroid hormone receptors and response to endocrine treatment. Eur J Cancer Clin Oncol 25: 459–467, 1989

    Google Scholar 

  14. Helle M, Hellin H, Antonen J, Krohn K: Human milk fat globule antigen IIID5, steroid receptors and histopathologic parameters in breast cancer. APMIS 96: 415–420, 1988

    Google Scholar 

  15. Domagala W, Lasota J, Dukowicz A, Markiewski M, Striker G, Weber K, Osborn M: Vimentin expression appears to be associated with poor prognosis in node-negative ductal NOS breast carcinomas. Am J Pathol 137: 1299–1304, 1990

    Google Scholar 

  16. Raymond WA, Leong AS: Co-expression of cytokeratin and vimentin intermediate filament proteins in benign and neoplastic breast epithelium. J Pathol 157: 299–306, 1989

    Google Scholar 

  17. Shousa S, Lysiottis T, Godfrey UM, Scheuer PJ: Carcinoembryonic antigen in breast cancer tissue: A useful prognostic indicator. Br Med J 1: 777–779, 1979

    Google Scholar 

  18. Walker RA: Immunohistochemistry of biological markers of breast carcinoma.In Delellis RA (ed) Advances in Immunohistochemistry. Masson Publishing, New York, 1984, pp 223–241

    Google Scholar 

  19. Lee AK, Rosen PP, Delellis RA, Saigo PE, Gangi MD, Groshen S, Bagin R, Wolfe HJ: Tumor marker expression in breast carcinomas and relationship to prognosis. Am J Clin Pathol 84: 687–696, 1985

    Google Scholar 

  20. Kuhajda FP, Offutt LE, Mendelsohn G: The distribution of carcinoembryonic antigen in breast carcinoma. Cancer 52: 1257–1264, 1983

    Google Scholar 

  21. Robertson JFR, Ellis IO, Bell J, Todd JH, Robbins A, Elston CW, Blamey RW: Carcinoembryonic antigen immunocytochemistry in primary breast cancer. Cancer 64: 1638–1645, 1989

    Google Scholar 

  22. Nap M, Keuning H, Burtin P, Oosterhuis JW, Fleuren G: CEA and NCA in benign and malignant breast tumors. Am J Clin Pathol 82: 526–534, 1984

    Google Scholar 

  23. Sheahan K, O'Brien MJ, Burke B, Dervan PA, O'Keane JC, Gottlieb LS, Zamchek N: Differential reactivities of carcinoembryonic antigen (CEA) and CEA-related monoclonal and polyclonal antibodies in common epithelial malignancies. Am J Clin Pathol 94: 157–164, 1990

    Google Scholar 

  24. Sommers CL, Walker-Jones D, Heckford SE, Worland P, Valverius E, Clark R, McCormick F, Stampfer M, Abularach S, Gelmann EP: Vimentin rather than keratin expression in some hormone-independent breast cancer cell lines and in oncogene-transformed mammary epithelial cells. Cancer Res 49: 4258–4263, 1989

    Google Scholar 

  25. Henzen-Logmans SC, Balm AJM, van der Waal I, Mullink H, Snow GB, Meyer CJLM: The expression of intermediate filaments and MAM-6 antigen in relation to the degree of morphologic differentiation of carcinoma of the head and neck: diagnostic implications. Otolaryngol Head Neck Surg 99: 539–547, 1988

    Google Scholar 

  26. Guelstein VI, Tchypysheva TA, Ermilova VD, Litvinova LV, Troyanovsky SM, Bannikov GA: Monoclonal antibody mapping of keratins 8 and 17 and of vimentin in normal human mammary gland, benign tumors, dysplasias and breast cancer. Int J Cancer 42: 147–153, 1988

    Google Scholar 

  27. Blum JL, Zeigler ME, Wicha MS: Regulation of mammary differentiation by the extracellular matrix. Environ Health Perspect 80: 71–83, 1989

    Google Scholar 

  28. Lesot H, Karcher-Djuricic V, Kubler MD, Ruch JV: Membrane-cytoskeleton interactions: inhibition of odontoblast differentiation by a monoclonal antibody directed against a membrane protein. Differentiation 37: 62–72, 1988

    Google Scholar 

  29. Bissell MJ, Ram TG: Regulation of functional cytodifferentiation and histiogenesis in mammary epithelial cells: role of the extracellular matrix. Environ Health Perspect 80: 61–70, 1989

    Google Scholar 

  30. Parry G, Beck JC, Moss L, Bartley J, Ojakian GK: Determination of apical membrane polarity in mammary epithelial cell cultures: the role of cell-cell, cell-substratum, and membrane-cytoskeleton interactions. Exp Cell Res 188: 302–311, 1990

    Google Scholar 

  31. Hass R, Giese G, Meyer G, Hartmann A, Dork T, Kohler L, Resch K, Traube P, Goppelt-Strube M: Differentiation and retrodifferentiation of U937 cell: reversible induction and suppression of intermediate filament protein synthesis. J Cell Biol 51: 265–271, 1990

    Google Scholar 

  32. Behren J: The role of cell adhesion molecules in cancer invasion and metastasis. Breast Cancer Res Treat 24: 175–184, 1993

    Google Scholar 

  33. Oka H, Shiozaki H, Kobayashi K, Inoue M, Tahara H, Kobayashi T, Takatsua Y, Matsuyoshi N, Hirano S, Takeichi M,et al.: Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res 53: 1696–1701, 1993

    Google Scholar 

  34. Moll R, Mitze M, Frixen UH, Birchmeier W: Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol 143: 1731–1742, 1993

    Google Scholar 

  35. Robey HL, Hiscott PS, Grierson I: Cytokeratins and retinal epithelial behaviour. J Cell Science 102: 329–340, 1992

    Google Scholar 

  36. Kartasova T, Roop DR, Yuspa SH: The relationship between the expression of differentiation-specific keratins 1 and 10 and cell proliferation in epidermal tumors. Mol Carcinogenesis 6: 18–25, 1992

    Google Scholar 

  37. Kurki P, Laasonen A, Tan EM, Lehtonen E: Cell proliferation and expression of cytokeratin filaments in F9 embryonal carcinoma cells. Development 106: 635–640, 1989

    Google Scholar 

  38. Kopan R, Fuchs E: The use of retinoic acid to probe the relation between hyperproliferation-associated keratins and cell proliferation in normal and malignant epidermal cells. J Cell Biol 109: 295–307, 1989

    Google Scholar 

  39. Larsimont D, Kiss R, d'Olne D, de Launoit Y, Mattheiem W, Paridaens R, Pasteels JL, Gompel C: Correlation between nuclear cytomorphometric parameters and estrogen receptor levels in breast cancer. Cancer 63: 2162–2168, 1989

    Google Scholar 

  40. Vic P, Garcia M, Humeau C, Rochefort H: Early effects of estrogen on chromatin ultrastructure in endometrial nuclei. Mol Cell Endocrinol 19: 79–92, 1980

    Google Scholar 

  41. Meyer JS, Ramanath BR, Stevens SC, White WL: Low incidence of estrogen receptor in breast carcinomas with rapid rates of cellular replication. Cancer 40: 2290–2298, 1977

    Google Scholar 

  42. Goodson WH, Ljung BM, Moore DH, Mayall B, Waldman FM, Chew K, Benz CC, Smith HS: Tumor labelling indices of primary breast cancers and their regional lymph node metastases. Cancer 71: 3914–3919, 1993

    Google Scholar 

  43. Meyer JS, Koehm S, Hughes JM, Higa E, Wittliff JL, Lagos JA, Manes JL: Bromodeoxyuridine labelling for S-phase measurement in breast carcinoma. Cancer 71: 3531–3540, 1993

    Google Scholar 

  44. Noguchi M, Thomas M, Koyasaki N, Ohta N, Taniya T, Kitagawa H, Miyazaki I, Mizukami Y: Influence of hormones on tumor growth, cell kinetics, estrogen receptor and insulinlike growth factor-I-related protein of human breast cancer (MCF-7) cells transplanted in nude mice. Mol Cell Endocrinol 92: 69–76, 1993

    Google Scholar 

  45. Jordan VC: Growth factor regulation by tamoxifen is demonstrated in patients with breast cancer. Cancer 72: 1–2, 1993

    Google Scholar 

  46. Freiss G, Prebois C, Vignon F: Control of breast cancer cell growth by steroids and growth factors: interactions and mechanisms. Breast Cancer Res Treat 27: 57–68, 1993

    Google Scholar 

  47. Dong XF, Berthois Y, Colomb E, Martin M: Cell cycle phase dependence of estrogen and epidermal growth factor (EGF) receptor expression in MCF-7 cells: implications in antiestrogen and EGF cell responsiveness. Endocrinol 129: 2719–2728, 1991

    Google Scholar 

  48. Bezwoda WL, Meyer K: The effect of α Interferon, 17 β Estradiol, and Tamoxifen on estrogen receptor concentration and cell cycle kinetics of MCF-7 cells. Cancer Res 50: 5387–5391, 1990

    Google Scholar 

  49. Berdichevsky F, Taylor-Papadimitriou J: Morphological differentiation of hybrids of human mammary epithelial cell lines is dominant and correlates with the pattern of expression of intermediate filaments. Exp Cell Res 194: 267–274, 1991

    Google Scholar 

  50. Sapino A, Pietribiasi F, Bussolati G, Marchisio PC: Estrogen and tamoxifen induced rearrangement of cytoskeletal and adhesion structures in breast cancer MCF-7 cells. Cancer Res 46: 2526–2551, 1986

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine, Central Hospital, 333 Sherbourne St., Toronto, Ontario, Canada

    C. David Bell & E. Marcella Tischler

  2. Department of Oncologic Pathology, the Ontario Cancer Institute, Toronto, Ontario, Canada

    Guy J. Laroye

  3. Department of Pathology, the Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

    C. David Bell, E. Marcella Tischler & Guy J. Laroye

Authors
  1. C. David Bell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Marcella Tischler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guy J. Laroye
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bell, C.D., Tischler, E.M. & Laroye, G.J. The relationship of cytoplasmic intermediate filaments and membrane antigens with hormone receptors, nuclear staining density, and mode of stromal invasion in human breast cancer. Breast Cancer Res Tr 33, 147–162 (1995). https://doi.org/10.1007/BF00682722

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00682722

Key words

Search

Navigation