Skip to main content
SpringerLink
Log in

Nuclear image analysis of immunohistochemically stained cells in breast carcinomas

  • Original Paper
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

Hitherto, the relationship between malignancy-associated morphological features in single tumour cells and the expression of markers indicating functional properties of these cells remained widely unknown. This study was aimed at describing differences in the size, shape and chromatin structure between tumour cells with different marker expression for progesterone receptors (PgR) and p53. Two series of breast cancers, consisting of 50 PgR-positive, and 39 p53-negative and 49 p53-positive mammary carcinomas, were investigated. The immunohistochemical staining was performed on paraffin sections using 3-amino-9-ethylcarbazole as the chromogenic substrate. By means of a cytometry workstation equipped with a computer-controlled motorised scanning stage, about 500 positive and negative tumour cells in each case were localised in the microscope and categorised by a scoring system for their staining intensity. After destaining, the tissue sections were Feulgen-stained. Then, all the tumour cells were relocated automatically and analysed by high resolution image cytometry. Among the numerous size, shape, and texture features used in the system, several variables of the nuclear contour and chromatin structure were found to be significantly different between the positive and negative tumour cell populations. Nuclei without PgR had more malignancy-associated morphological features than PgR-positive cells. Whereas p53-negative nuclei had a higher degree of regularity, their positive counterparts exhibited higher DNA ploidy values.

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

Similar content being viewed by others

References

  • Allred CG, Clark GM, Elledge R, Fuqua SAW, Brown RW, Chamness GC, Osborne CK, McGuire WL (1993) Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst 85:200–206

    PubMed  Google Scholar 

  • Auer G, Eriksson E, Azavedo E, Caspersson T, Wallgren A (1984) Prognostic significance of nuclear DNA content in mammary adencarcinomas in humans. Cancer Res 44:394–396

    PubMed  Google Scholar 

  • Auer GU, Heselmeyer KM, Steinbeck RG, Munck-Wikland E, Zetterberg AD (1994) The relationship between aneuploidy and p53 over expression during genesis of colorectal adenocarcinoma. Virchows Arch 424:343–347

    PubMed  Google Scholar 

  • Barnes DM, Dublin EA, Fisher CJ, Levison DA, Millis RR (1993) Immunohistochemical detection of p53 protein in mammary carcinoma: an important new independent indicator of prognosis? Hum Pathol 24:469–476

    PubMed  Google Scholar 

  • Battifora H (Ed) (1994) p53 Immunohistochemistry: a word of caution. Hum Pathol 25:435–437

    Google Scholar 

  • Bloom HJG, Richardson WW (1957) Histologic grading and prognosis in breast cancer. Br J Cancer 11:359–377

    PubMed  Google Scholar 

  • Bosari S, Lee AKC, Viale G, Heatley GJ, Coggi G (1992) Abnormal p53 immunoreactivity and prognosis in node-negative breast carcinomas with long-term follow up. Virchows Arch 421:291–295

    Google Scholar 

  • Cattoretti G, Rilke F, Andreola S, Amato LD, Delia D (1988) p53 expression in breast cancer. Int J Cancer 41:178–183

    PubMed  Google Scholar 

  • Clark GM, McGuire WL, Hubay CA (1983) Progesterone receptors as a prognostic factor in stage 2 breast cancer. N Engl J Med 309:1343–1347

    PubMed  Google Scholar 

  • Davidoff AM, Herndon JE, Glover NS, Kerns B-JM, Pence JC, Iglehart JD, Marks JR (1991) Relation between p53 overexpression and established prognostic factors in reast cancer. Surgery 110:259–264

    PubMed  Google Scholar 

  • Domagala W, Harezga B, Szadowska A, Markiewski M, Weber K, Osborn M (1993) Nuclear p53 protein accumulates preferentially in medullary and high-grade ductal but rarely in lobular breast carcinomas. Am J Pathol 142:669–674

    PubMed  Google Scholar 

  • Friedrich K, Dimmer V, Haroske G, Loßnitzer A, Kasper M, Theissig F, Kunze KD (1995) Expression of p53 and bcl-2 in correlation to clinicopathological parameters, hormone receptor status and DNA ploidy in breast cancers. Pathol Res Pract (in press)

  • Gazitt Y, Erdos GW (1994) Fluctuations and ultrastructural localization of oncoproteins and cell cycle regulatory proteins during growth and apoptosis of synchronized AGF cells. Cancer Res 54:950–956

    PubMed  Google Scholar 

  • Göhring U-J, Heckel C, Vierbuchen M, Titius B, Scharl A (1993) Der immuhistochemische Nachweis des p53-Proteins in Paraffin eingebetteten Geweben primärer humaner Mammakarzinome und seine klinische Wertigkeit. Verh Dtsch Ges Pathol 77:302

    Google Scholar 

  • Haroske G, Meyer W, Dimmer V, Kunze KD, Theissig F (1993) Feasibility and limitations of a cytometric DNA ploidy analysis in tissue sections. Zentralbl Pathol 149:407–419

    Google Scholar 

  • Haroske G, Meyer WD, Theissig F, Kunze KD (1995) Increase of precision and accuracy of DNA cytometry by correcting diffraction and glare errors. Anal Cell Pathol 9:1–12

    PubMed  Google Scholar 

  • Hurlimann J (1993) Prognostic value of p53 protein expression in breast carcinomas. Pathol Res Pract 189:996–1003

    PubMed  Google Scholar 

  • WHO (1981) International histological classification of tumors. Histological typing of breast tumours. 2nd edn., WHO: Geneva

    Google Scholar 

  • Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51:6304–6311

    PubMed  Google Scholar 

  • Kunze KD, Haroske G, Dimmer V, Meyer W, Theissig F (1989) Grading and prognosis of invasive ductale mammary carcinoma by nuclear image analysis in tissue sections. Pathol Res Pract 185:689–693

    PubMed  Google Scholar 

  • Lane DP (1992) p53, guardian of the genome. Nature 358:15–16

    PubMed  Google Scholar 

  • Levine AJ, Momand J, Finlay CA (1991) The p53 tumour suppressor gene. Nature 351:453–456

    PubMed  Google Scholar 

  • Lipponen P, Ji H, Aaltomaa S, Syrjõnen S, Syrjõnen K (1993) p53 protein expression in breast cancer as related to histopathological characteristics and prognosis. Int J Cancer 55:51–56

    PubMed  Google Scholar 

  • Mattfeldt T, Neurohr W, Müller A, Klinga K (1985) Morphometrische Korrelate des Steroidrezeptorgehaltes duktal-invasiver Mammakarzinome. Verh Dtsch Ges Pathol 69:350–355

    PubMed  Google Scholar 

  • Miller C, Koeffler HP (1993) p53 mutations in human cancer. Leukemia 7 [Suppl 2]:18–21

    Google Scholar 

  • Ostrowski JL, Sawan A, Henry L, Wright C, Hennessy C, Lennard TJW, Agnus B, Horne CHW (1991) p53 expression in human breast cancer related to survival and prognostic factors: an immunohistochemical study. J Pathol 164:75–81

    PubMed  Google Scholar 

  • Porter PL, Gown AM, Kramp SG, Coltrera MD (1992) Widespread p53 overexpression in human malignant tumors. Am J Pathol 140:145–153

    PubMed  Google Scholar 

  • Quiao L, Peihong W, Ghaleb AH, Pizzolo JG, Miller TB, Melamed MR (1994) Bivariate flow cytometric analysis of p53 and DNA content in hepatocellular carcinoma. Anal Quant Cytol Histol 16:124–130

    PubMed  Google Scholar 

  • Remmele W, Stegner HE (1987) Vorschlag zur einheitlichen Definition eines Immunreaktiven Score (IR) für den immun-histochemischen Estrogenrezeptor-Nachweis (ER-IRA) im Mammakarzinomgewebe. Pathologe 8:138–140

    PubMed  Google Scholar 

  • Schenk U, Burger G, Jütting U, Peters-Welte C, Eiermann W (1985) Punktionszytologie der Mamma: Korrelation visueller und bildanalytischer Untersuchungen mit dem Hormonrezeptorstatus. Geburtshilfe Frauenheilkd 45:17–21

    PubMed  Google Scholar 

  • Schenk U, Eiermann W, Burger G, Gais P, Jütting U, Rodenacker K, Schenk UB (1987) Visual and cytometric grading of breast carcinoma specimens: correlations with the hormone receptor status. Academic Press. London, pp 407–410

    Google Scholar 

  • Silvestrini R, Benini E, Daidone MG, Veneroni S, Borachi P, Cappelletti V, Fronzo G di, Veronesi U (1993) p53 as an independent prognostic marker in lymph node-negative breast cancer patients. J Natl Cancer Inst 85:965–970

    PubMed  Google Scholar 

  • Singh S, Simon M, Meybohm I, Jantke I, Maass H, Goedde HW (1993) Human breast cancer: Frequent p53 allele loss and protein overexpression. Hum Genet 90:635–640

    PubMed  Google Scholar 

  • Stegner H-E, Jonat W, Mass H (1986) Immunihistochemischer Nachweis nukleärer Östrogenrezeptoren mit monoklonalen Antikörpern in verschiedenen Typen des Mammakarzinoms. Pathologe 7:156–163

    PubMed  Google Scholar 

  • Thomas DB (1986) Hormones and hormone receptors in the etiology of breast cancer. Breast Cancer Res Treat 7:S11-S22

    PubMed  Google Scholar 

  • Vojtesek B, Bartek J, Midgley CA, Lane DP (1992) An immunochemical analysis of the human nuclear phosphoprotein p53. New monoclonal antibodies and epitope mapping using recombinant p53. J Immunol Methods 151:237–244

    PubMed  Google Scholar 

  • Weinert T, Lydall D (1993) Cell cycle checkpoints genetic instability and cancer. Semin Cancer Biol 4:129–140

    PubMed  Google Scholar 

  • Wynford-Thomas D (1992) P53 in tumour pathology: can we trust immunocytochemistry? J Pathol 166:329–330

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pathology, Technical University Dresden, Fetscherstrasse 74, D-01307, Dresden, Germany

    G. Haroske, V. Dimmer, Katrin Friedrich, W. Meyer, Berit Thieme, F. Theissig & K. D. Kunze

Authors
  1. G. Haroske
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. Dimmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katrin Friedrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W. Meyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Berit Thieme
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. Theissig
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K. D. Kunze
    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

Haroske, G., Dimmer, V., Friedrich, K. et al. Nuclear image analysis of immunohistochemically stained cells in breast carcinomas. Histochem Cell Biol 105, 479–485 (1996). https://doi.org/10.1007/BF01457662

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01457662

Keywords

Search

Navigation