Summary
The general background to tumour analytic work using quantitative optical cytochemical methods is first presented. An instrument complex, constructed especially for multiparameter work in cytopathological material has been developed. Nuclear changes have been followed in cell populations during their development through different grades of atypia to cancer and conspicuous cytochemical changes were observed.
In a comprehensive series of clinically verified mammary carcinomas, a large percentage of cases was found in which the DNA values were within the normal range, while the others showed pronounced aneuploidy. A clear correlation was found between DNA profile-type and patient survival, the latter of which reflects the degree of malignancy in the individual case.
The shift from resting state (G0) to growth activated G1-stage is initiated by a large increase of the nuclear proteins. Mammary tumours of a high malignancy grade, as judged by their DNA profile type, showed an especially great accumulation of nuclear protein and thus a high degree of activation.
DNA-profile measurements, preferably combined with determinations of nuclear proteins can thus be used for judging malignancy grades in mammary tumours, which is also of considerable clinical interest. An as yet limited observational material also indicates similar situations in some other types of tumour.
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References
Atkin, N. B. (1972) Modal deoxyribonucleic acid value and survival in carcinoma of the breast.Br. Med. J. 86, 271–2.
Auer, G. (1972a) Nuclear protein content and DNA-histone interaction.Expl Cell Res. 75, 231–6.
Auer, G. (1972b)Cytochemical properties of chromatin related to changes in cellular growth activity. Thesis, Almqvist & Wiksell, Stockholm.
Auer, G., Caspersson, T. &Wallgren, A. (1980) DNA content and survival in mammary carcinoma.Analyt. Quant. Cytol. 2, 161–5.
Auer, G., Moore, G., Ringertz, N. R. &Zetterberg, A. (1973) DNA-dependent RNA synthesis in nuclear chromatin of fixed cells.Expl Cell Res. 76, 229–33.
Auer, G., Ono, J., Nasiell, M., Caspersson, T., Kato, H., Konaka, C. &Hayata, Y. (1982) Reversibility of bronchial cell atypia.Cancer Res. 42, 4241–7.
Auer, G. &Zetterberg, A. (1972) The role of nuclear proteins in RNA synthesis.Expl Cell Res. 75, 245–53.
Bolund, L. (1971)Cytochemical properties of chromatin and nuclei in relation to genome activation and repression. Thesis, Balder AB, Stockholm.
Böhm, N. &Sandritter, W. (1975) DNA in human tumors. A cytophotometric study.Curr. Top. Pathol. 60, 151–219.
Caspersson, O. (1964) Quantitative cytochemical studies on normal, malignant, premalignant and atypical cell populations from the human uterine cervix.Acta cytologica,8, 45–60.
Caspersson, T. (1936) Uber den chemischen Aufbau der Strukturen des Zellkernes.Skand. Arch. Physiol. 73, Suppl. 8.
Caspersson, T. (1940) Die Eiweissverteilung in den Strukturen des Zellkernes.Chromosoma 1, 562–604.
Caspersson, T. (1941) Studien über den Eiweissumsatz der Zelle.Naturwissenschaften 29, 33–43.
Caspersson, T. (1950)Cell Growth and Cell Function. New York: W. W. Horton & Co. Inc.
Caspersson, T. (1979) Quantitative tumor cytochemistry.Cancer Res. 39, 2341–55.
Caspersson, T. (1973) InChromosome Identification: Techniques and Applications in Biology and Medicine (edited byCaspersson, T. andZech, L.), Nobel Symposium No. 23, pp. 50–55. New York, London: Academic Press.
Caspersson, T. &Kudynowski, J. (1980) Cytochemical instrumentation for cytopathological work.Int. Rev. exp. Path. 21, 1–54.
Caspersson, T., Lindsten, J., Lomakka, G., Möller, A. &Zech, L. (1972) The use of fluorescence techniques for the recognition of mammalian chromosomes and chromosome regions.Int. Rev. exp. Path. 21, 1–72.
Caspersson, T. &Lomakka, G. (1962) Scanning microscopy techniques for high resolution quantitative cytochemistry.Ann. N.Y. Acad. Sci. 97, 449–63.
Caspersson, T. &Lomakka, G. (1970) Recent progress in quantitative cytochemistry: Instrumentation and results. InIntroduction to Quantitative Cytochemistry II (edited byWied, G. L. andBahr, G. F.), pp. 27–56. New York, London: Academic Press.
Caspersson, T., Lomakka, G. &Svensson, G. A. (1957) A coordinated set of instruments for optical quantitave high resolution cytochemistry.Expl Cell Res., Suppl.4, 9–24.
Caspersson, T. & Santesson, L. (1942) Studies of protein metabolism in the cells of epithelial tumors.Acta radiol., Suppl. 46.
Caspersson, T., Zech, L. &Johansson, C. (1970a) Analysis of the human metaphase chromosome set by aid of DNA-binding fluorescent agents.Expl Cell Res. 62, 490–2.
Caspersson, T., Zech, L., Johansson, C. &Modest, E. J. (1970b) Identification of human chromosomes by DNA-binding fluorescing agents.Chromosoma 30, 215–27.
Gahrton, G. (1966)Quantitative cytochemical studies on normal and leukemic leukocytes. Thesis, Balder AB, Stockholm.
Gaub, J. (1981) Quantification of nuclear non-histone proteins by Feulgen-Naphtol Yellow S cytophotometry.Histochem. J. 13, 717–22.
Gaub, J., Auer, G. &Zetterberg, A. (1975) Quantitative cytochemical aspects of a combined Feulgen naphtol yellow S staining procedure for the simultaneous determination of nuclear and cytoplasmic proteins and DNA in mammalian cells.Expl Cell Res. 92, 323–32.
Gledhill, B. L. (1966) Studies on the DNA content, dry mass and optical area of bull spermatozoal heads during epididymal maturation.Acta vet. scand. 7, 131–42.
Konaka, C., Auer, G., Nasiell, M., Hayata, Y., Kato, H., Caspersson, T. &Ono, J. (1982a) Sequential cytomorphological and cytochemical changes during development of bronchial carcinoma in beagle dogs exposed to 20-methylcholanthrene.Acta histochem. cytochem. 15, 779–97.
Konaka, C., Auer, G., Nasiell, M., Kato, H., Hayashi, N., Ono, J., Hayata, Y. &Caspersson, T. (1982b) Pathogenesis of squamous bronchial carcinoma in 20-methyl-cholanthrene-treated dogs.Analyt. quant. Cytol. 4, 61–71.
Kreicbergs, A., Zetterberg, A. &Söderberg, G. (1980) The prognostic significance of nuclear DNA-content in chondrosarcoma.Analyt. Quant. Cytol. 2, 272–9.
Mitelman, F. &Levan, G. (1981) Clustering of aberrations to specific chromosomes in human neoplasms. IV. A Survey of 1871 cases.Hereditas 95, 79–139.
Moberger, G. (1954) Malignant transformation of squamous epithelium. A cytochemical study with special reference to cytoplasmic nucleic acids and proteins.Acta radiologica, Suppl. 112.
Moore, G. P., Auer, G. &Zetterberg, A. (1974) Reactivation of nuclear RNA polymerase activity in growth stimulated epithelial cells.Expl Cell Res. 88, 375–81.
Zetterberg, A. &Esposti, P. L. (1980) Prognostic significance of nuclear DNA levels in prostatic carcinoma.Scand. J. Urol. Nephrol. 55, 53–8.
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TheHistochemical Journal Lecture for 1982 given by Professor Caspersson at a Symposium on ‘Nuclear Histochemistry and Differentiation’, organized by the Histochemistry and Cytochemistry Section of the Royal Microscopical Society, in London on 13 July 1982.
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Caspersson, T., Auer, G., Fallenius, A. et al. Cytochemical changes in the nucleus during tumour development. Histochem J 15, 337–362 (1983). https://doi.org/10.1007/BF01002968
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DOI: https://doi.org/10.1007/BF01002968