Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-29T13:02:55.291Z Has data issue: false hasContentIssue false

A comparison of cellular proliferation markers in squamous cell carcinoma of the head and neck

Published online by Cambridge University Press:  29 June 2007

A. S. Jones*
Affiliation:
Departments of Otolaryngology/Head and Neck Surgery, University of Liverpool.
N. J. Roland
Affiliation:
Departments of Otolaryngology/Head and Neck Surgery, University of Liverpool.
A. W. Caslin
Affiliation:
Departments of Pathology, University of Liverpool.
T. G. Cooke
Affiliation:
Departments of Surgery and Otolaryngology, University of Glasgow.
L. D. Cooke
Affiliation:
Departments of Surgery and Otolaryngology, University of Glasgow.
G. Forster
Affiliation:
Departments of Surgery and Otolaryngology, University of Glasgow.
*
Professor A.S. Jones, Department Otorhinolaryngology, University of Liverpool, Royal Liverpool Hospital, P. O. Box 147, Liverpool L69 3BX.

Abstract

Head and neck squamous cell carcinoma has a relatively good prognosis but treatment may be at the expense of function and quality of life. Various host and tumour parameters have been studied in an attempt to predict the course of the disease but without success. It has been hoped that laboratory based methods, particularly those based on molecular biology, may prove more useful. Cell kinetic parameters are studied in this paper.

The present study includes 75 patients with a proven squamous cell carcinoma of the head and neck at various sites and undergoing various forms of treatment. The patient's mean age was 62 years and the median survival rate 45 months. Immunohistochemical techniques using Ki67 and PCNA were compared with flow cytometric analysis which included the BRDU labelling index, the duration of S phase, ploidy and potential doubling time.

The median PCNA index was 560 and the Ki67 index 298. These indices varied between 980 and 150 for PCNA and 808 and 110 for Ki67. The BRDU labelling index measured by flow cytometry was 8.9 with a range from 25 to 1.6 and the duration of S phase was 14.8 hours. The PCNA index failed to correlate with any host or tumour factors and this failure was also seen in Ki67 indices and also in the flow cytometric parameters. There was a strong correlation between PCNA and Ki67 expression (p<0.0001). Neither PCNA nor Ki67 values were significantly different between irradiated and nonirradiated tissues nor in sites or in patients who later developed lymph node metastases. Neither PCNA nor any other cell kinetics parameter correlated with survival and multivariate analysis confirmed this lack of correlation.

The PCNA labelling index like the Ki67 index and flow cytometric parameters does not appear to be of value in predicting the course of squamous cell carcinoma of the head and neck.

Type
Main Articles
Copyright
Copyright © JLO (1984) Limited 1994

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

American Joint Committee (AJC) for Cancer staging and End Results Reporting (1972) Clinical Staging System for Carcinoma of the Larynx, American Joint Committee, Chicago.Google Scholar
Armitage, P., Berry, G. (1987). Statistical Methods in Medical Research, 2nd Edition, London, Blackwell Scientific Publications, pp 436437.Google Scholar
Begg, A. C., McNally, N. J., Shrieve, D. C., Karcher, H. (1985) A method to measure the duration of DNA synthesis and the potential doubling time from a single sample. Cytometry 6: 620626.CrossRefGoogle ScholarPubMed
Bennett, M. H., Wilson, G. D., Dische, S., Saunders, M. I., Martindale, C. A., Robinson, B. M., OHalloran, A. E., Leslie, M. D., Laing, J. H. E. (1992) Tumour proliferation assessed by combined histological and flow cytometric analysis: implications for therapy in squamous cell carcinoma of the head and neck. British Journal of Cancer 65: 870878.CrossRefGoogle Scholar
Bravo, R., Celis, J. E. (1980) A search for differential polypeptide synthesis throughout the cell cycle of HeLa cells. Journal of Cell Biology 84: 795802.CrossRefGoogle ScholarPubMed
Celis, J. E., Celis, A. (1985) Cell cycle dependent variations in the distribution of the nuclear protein cyclin (proliferating cell nuclear antigen) in cultured cells: subdivision of S phase. Proceedings of the National Academy of Science USA 82: 32623266.CrossRefGoogle ScholarPubMed
Chalkley, H. W. (1943) Method for the quantitative morphologic analysis of tissues. Journal of the National Cancer Institute 4: 4753.Google Scholar
Cooke, L. D., Cooke, T. G., Forster, G., Jones, A. S., Stell, P. M. (1994) Prospective evaluation of cell kinetics in head and neck squamous carcinoma: the relationship to tumour factors and survival. British Journal of Cancer 69: 717720.CrossRefGoogle ScholarPubMed
Cox, D. R. (1972) Regression models and life-tables. Journal of the Royal Statistical Society B34: 187220.Google Scholar
Falini, B., Flenghi, L., Fagioli, M., Stein, H., Schwarting, R., Riccardi, C., Manocchio, I., Piled, S., Telicci, P. S., Lanfrancone, L. (1989) Evolutionary conservation in various mammalian species of the human proliferation assocaited epitope recognized by the Ki67 monoclonal antibody. Journal of Histochemistrx and Cytochemistry 37: 14711473.CrossRefGoogle Scholar
Forster, G., Cooke, T. G., Cooke, L. D., Stanton, P. D., Bowie, G., Stell, P. M. (1992) Tumour growth rates in squamous carcinoma of the head and neck measured by in vivo bromodeoxyuridine incorporation and flow cytometry. British Journal of Cancer 65: 698702.CrossRefGoogle ScholarPubMed
Frank, J. L., Lawrence, W., Banks, W. L., McKinnon, J. G., Chan, W. M.Collins, W. M. (1992) Modulation of cell cycle kinetics in human cancer with total parenteral nutrition. Cancer 69: 18581864.3.0.CO;2-H>CrossRefGoogle ScholarPubMed
Galand, P., Degraef, C. (1989) Cyclin/PCNA immunostaining as an alternative to tritiated thymidine pulse labelling for marking S phase cells in paraffin sections from animal and human tissues. Cell and Tissue Kinetics 22: 383392.Google Scholar
Gerdes, J., Schwab, U., Lemke, H., Stein, H. (1983) Production of a monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. International Journal of Cancer 31: 1320.CrossRefGoogle ScholarPubMed
Gerdes, J., Lemke, H., Baisch, H., Wacker, H. H., Schwab, U., Stein, H. (1984) Cell cycle analysis of a cell proliferation associated human nuclear antigen defined by the monoclonal antibody Ki67. Immunology 133: 17101716.Google Scholar
Gerdes, J., Lelle, R. J., Pickartz, H., Heidenreich, W., Schwarting, R., Kurtsiefer, L., Stauch, G., Stein, H. (1986) Growth fractions in breast cancers determined in situ with monoclonal antibody Ki67. Journal of Clinical Pathology 39: 977980.CrossRefGoogle Scholar
Hall, P. A., Levison, D. A. (1990) Review: assessment of cell proliferation in histological material. Journal of Clinical Pathology 43: 184192.CrossRefGoogle ScholarPubMed
Hirano, T., Zitsch, R. P., Gluckman, J. L. (1991) The use of bromodeoxyuridine cytokinetic studies as a prognostic indicator of cancer of the head and neck. Laryngoscope 101: 130133.CrossRefGoogle ScholarPubMed
Howard, A., Pelc, S. R. (1951) Nuclear incorporation of 32P as demonstrated by autoradiographs. Experimental Cell Research 2: 178187.CrossRefGoogle Scholar
Isola, J. J., Helin, H. J., Helle, M. J., Olli-Pekka, K. (1990) Evaluation of cell proliferation in breast carcinoma. Comparison of Ki67 immunohistochemical study, DNA flow cytometric analysis, and mitotic count. Cancer 65: 11801184.3.0.CO;2-7>CrossRefGoogle ScholarPubMed
Jain, S., Filipe, M. I., Hall, P. A., Waseem, N. H., Lane, D. P., Levison, D. A. (1991) Proliferating cell nuclear antigen (PCNA) prognostic value in gastric carcinoma. Journal of Clinical Pathology 44: 655659.CrossRefGoogle ScholarPubMed
Jaskulski, D., DeRiel, J. K., Mercer, W. E., Calabretta, B., Baserga, R. (1988) Inhibition of cellular proliferation by antisense oligodeoxynucleotides to PCNA cyclin. Science 240: 15441546.CrossRefGoogle ScholarPubMed
Katz, A. E. (1983) Immunobiologic staging of patients with carcinoma of the head and neck. Laryngoscope 93: 445466.CrossRefGoogle ScholarPubMed
McCormick, D., Yu, C., Hobbs, C., Hall, P. A. (1993) The relevance of antibody concentration to the immunohistochemical quantification of cell proliferation-associated antigens. Histopathology 22: 543547.CrossRefGoogle Scholar
Mendelsohn, M. L.(1962) Autoradiographic analysis of cell proliferation in spontaneous breast cancer of C3H mouse. Ill: The growth fraction. Journal of the National Cancer Institute 28: 10151029.Google Scholar
Moriuchi, T., Matsumato, K., Koji, T., Nakane, P. K. (1986) Molecular cloning and nucleotide sequence analysis of rat PCNA/cyclin cDNA. Nucleic Acid Symposia Series 17: 117120.Google Scholar
Morris, G. F., Mathews, M. B. (1989) Regulation of proliferating cell nuclear antigen during the cell cycle. Journal of Biological Chemistry 264: 1385613864.CrossRefGoogle ScholarPubMed
Peto, R., Pyke, M. A., Armitage, P., Breslow, M. E., Cox, D. R., Howard, S. V., Mantel, N., McPherson, K., Peto, J., Smith, P. G. (1977) Design and analysis of randomized clinical trials requiring prolonged observations of each subject. British Journal of Cancer 35: 139.CrossRefGoogle Scholar
Porschen, R., Lohe, B., Hengels, K. J., Borchard, F. (1989) Assessment of cell proliferation in colorectoral carcinomas using the monoclonal antibody Ki67: correlation with pathohistologic criteria and influence of radiation. Cancer 64: 25012505.3.0.CO;2-0>CrossRefGoogle Scholar
Prelich, G., Tan, C. K., Kostura, M., Mathews, M. B., So, A. S., Downey, K. M., Stillman, B. (1987) Functional identify of proliferating cell nuclear antigen and a DNA polymerase-delta auxiliary protein. Nature 326: 517520.CrossRefGoogle Scholar
Quastler, H., Sherman, F. G. (1959) Cell population kinetics in the intestinal epithelium of the mouse. Experimental Cell Research 17: 420438.CrossRefGoogle ScholarPubMed
Riccardi, A., Danova, M., Wilson, G., Ucci, G., Dormer, P., Mazzini, G., Brugnatelli, S., Girino, M., McNally, N. J., Ascari, E. (1988) Cell kinetics in human malignancies studied with in vivo administration of bromodeoxyuridine and flow cytometry. Cancer Research 48: 62386245.Google ScholarPubMed
Roland, N. J., Caslin, A. W., Bowie, G. L., Jones, A. S. (1994) Has the cellular proliferation marker Ki67 any clinical relevance in squamous cell carcinoma of the head and neck? Clinical Otolaryngology 19: 1318.CrossRefGoogle ScholarPubMed
Roland, N. J., Caslin, A. W., Nash, J., Stell, P. M. (1994) A preliminary assessment of markers of cellular proliferation in squamous cell carcinoma of the head and neck. Clinical Oncology (in press).Google Scholar
Sabattini, E., Gerdes, J., Gherlinzoni, F., Poggi, S., Zucchini, P., Melilli, G., Grigioni, F., Del Vecchio, M. T., Leoncini, L., Falini, B., Pileri, S. A. (1993) Comparison between the monoclonal antibodies Ki67 and PC 10 in 125 malignant lymphomas. Journal of Pathology 169: 397403.CrossRefGoogle Scholar
Steel, G. G. (1977) Growth Kinetics of Tumours. London/Oxford. University Press.Google Scholar
UICC (1987) TNM Classification of Malignant Tumours, 4th Edition, (Hermanek, P., Sobin, L. H., eds.). Springer-Verlag. Heidelberg.CrossRefGoogle Scholar
Van Dierendonck, J. H., Keijezer, R., van de Velde, C. J. K., Cornelisse, C. J. (1989) Nuclear distribution of the Ki67 antigen during the cell cycle: comparison with growth fraction in human breast cancer cells. Cancer Research 49: 29993002.Google ScholarPubMed
Verhuijen, R., Kuipers, H. J. H., Schlingemann, R. O., Boehmer, A. L. M., Van Driel, R., Brakenhoff, G. J., Ramaekers, F. C. S. (1989a) Ki67 detects a nuclear matrix-associated proliferationrelated antigen. I: Intracellular localization during interphase. Journal of Cell Science 92: 123125.CrossRefGoogle Scholar
Verhuijen, R., Kuipers, H. J. H., Van Driel, R., Beck, J. L. M., van Dierendonck, J. H., Brakenhoff, G. J., Ramaekers, F. C. S. (1989b) Ki67 detects a nuclear matrix-associated proliferationrelated antigen. II: Localization in mitotic cells and association with chromosomes. Journal of Cell Science 92: 531532.CrossRefGoogle Scholar
Waseem, N. H., Lane, D. P. (1990) Monoclonal antibody analysis of the proliferating cell nuclear antigen (PCNA). Journal of Cell Science 96: 121129.CrossRefGoogle ScholarPubMed
Wilson, G. D. (1991) Assessment of human tumour proliferation using bromodeoxyuridine – current status. Acta Oncologica 30 (8): 903910.CrossRefGoogle ScholarPubMed
Woods, A. L., Hall, P. A., Shepherd, N. H., Hanby, A. M., Wassem, N. H., Lane, D. P., Levison, D. A. (1991) The assessment of proliferating cell nuclear antigen (PCNA) immunostaining in primary gastro-intestinal lymphomas and its relationship to histological grade S + G:M phase fraction (flow cytometric analysis) and prognosis. Histopathology 19: 2127.CrossRefGoogle Scholar
Yonemura, Y., Ooyama, S., Sugiyama, K., Ninomiya, I., Kamata, T., Yamaguchi, A., Matsumoto, H., Miyazaki, I. (1990) Growth fractions in gastric carcinomas determined with monoclonal antibody Ki67. Cancer 65: 11301134.3.0.CO;2-A>CrossRefGoogle Scholar
Yu, C. C. W., Hall, P. A., Fletcher, C. D. M., Camplejohn, R. S., Waseem, N. H., Lane, D. P., Levison, D. A. (1991) Haemangiopericytomas. The prognostic value of immunohistochemical staining with a monoclonal antibody to proliferating cell nuclear antigen. Histopathology 19: 2933.CrossRefGoogle ScholarPubMed
Zarbo, R. J., Crissman, J. D. (1988) The surgical pathology of head and neck cancer. Seminars in Oncology 15: 1011.Google ScholarPubMed