Summary
Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the late G1 and S phase of the cell cycle and immunohistochemical detection of the protein represents a useful marker for the proliferating fraction of cells in tissue specimens. A series of malignant and pre-malignant lesions of the oral cavity and skin were evaluated by the streptavidin biotin immunoperoxidase method for detection of this protein. Monoclonal anti-PCNA antibody (PC 10) labelled proliferating cells in all cases with varying intensity of nuclear staining. In squamous cell carcinoma (n=48), PCNA positivity correlated with the differentiation and atypia of the tumour cells; however, in poorly differentiated tumours, the relationship between PCNA expression and proliferation was lost. Basal cell carcinoma showed an increased growth fraction in tiny epithelial nests (mean 43.8, SD 6.0,n=20) than in neoplastic basal cells (mean 30.1, SD 6.9,n=8). The growth fractions were significantly higher in the pre-malignant lesions (leukoplakia, mean 22.3, SD 7.7,n=14; Bowen's disease, mean 45.2, SD 11.7,n=12; senile keratosis, mean 41.2, SD 7.0,n=12) than in the normal mucosa (mean 9.8, SD 4.9,n=10), suggesting that cellular growth fractions correlate with the degree of dysplasia in pre-malignant lesions.
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Almendral JM, Huebsch D, Blundell PA, Macdonald-Bravo H, Bravo R (1987) Cloning and sequence of human nuclear protein cyclin: homology with DNA binding proteins. Proc Natl Acad Sci USA 84:1575–1579
Battersby S, Anderson TJ (1990) Correlation of proliferative activity in breast tissue using PCNA/cyclin. Hum Pathol 21:781
Bravo R, Frank R, Blundell PA, Macdonald-Bravo H (1987) Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature 309:515–520
Coltrera MD, Gown AM (1991) PCNA/cyclin expression and BrdU uptake define different subpopulations in different cell lines. J Histochem Cytochem 39:23–30
Dawson AE, Norton JA, Weinberg DS (1990) Comparative assessment of proliferation and DNA content in breast carcinoma by image analysis and flow cytometry. Am J Pathol 136:1115–1124
Dierendock JHV van, Wijsman RK, Keizer R, Velde CJH van de, Cornelisse CJ (1991) Cell cycle related staining patterns of anti-proliferating cell nuclear antigen monoclonal antibodies: comparison with BrdU labeling and Ki-67 staining. Am J Pathol 138:1165–1172
Garcia RL, Coltrera MD, Gown AM (1989) Analysis of proliferative grade using PCNA/cyclin monoclonal antibodies in fixed, embedded tissues-comparison with flow cytometric analysis. Am J Pathol 134:733–739
Hall PA, Levison DA, Woods AL, Yu CC-W, Kellock DB, Watkins JA, Barnes DM, Gillett CE, Camplejohns R, Dover R, Waseem NH, Lane DP (1990) Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol 162:285–294
Hitchcock C (1991) Ki-67 staining as a means to simplify analysis of tumor cell proliferation. Am J Clin Pathol 96:444–446
Jaskulski D, deRiel JK, Mercer WE, Calabretta B, Baserga R (1988) Inhibition of cellular proliferation by antisense oligo-deoxynucleotides to PCNA/cyclin. Science 240:1544–1546
Kurki P, Vanderlaan M, Dolbeare F, Grey J, Tan EM (1986) Expression of proliferating cell nuclear antigen (PCNA/cyclin) during the cell cycle. Exp Cell Res 166:209–219
Kurki P, Ogata K, Tan EM (1988) Monoclonal antibodies to prolife-rating cell nuclear antigen (PCNA/cyclin) as probes for proliferating cells by immunofluorescence microscopy and flow cytometry. J Immunol Methods 109:49–59
Landberg G, Tan EM, Ross G (1990) Flowcytometric multiparameter analysis of proliferating cell nuclear antigen/cyclin and Ki-67 antigen: a new view of the cell cycle. Exp Cell Res 187:111–118
Miyachi K, Fritzler MJ, Tan EM (1978) Autoantibody to a nuclear antigen in proliferating cells. J Immunol 121:2228–2234
Morris GF, Mathews MB (1989) Regulation of proliferating cell nuclear antigen during cell cycle. J Biol Chem 264:13856–13864
Prelich G, Kostura M, Marshak DR, Mathews MB, Stillman B (1987a) The cell cycle regulated proliferating cell nuclear antigen is requires for SV 40 DNA replication in vitro. Nature 326:471–475
Prelich G, Tan CK, Kostura M, Marshak DR, Mathews MB, So AG, Downey KM, Stillman B (1987b) Functional identity of proliferating cell nuclear antigen and DNA polymerase delta auxiliary protein. Nature 326:517–520
Robbins BA, Vega D de la, Ogata K, Tan EM, Nakamura RM (1987) Immunohistochemical detection of proliferating cell nuclear antigen in solid human malignancies. Arch Pathol Lab Med 111:841–845
Smetana K, Gyorkey F, Chan PK, Tan E, Busch H (1983) Proliferating cell nuclear antigen (PCNA) and human malignant tumor nucleolar antigens (HMTNA) in nucleoli of human hematological malignancies. Blut 46:133–141
Takasaki Y, Robinson WA, Tan EM (1984) Proliferating cell nuclear antigen in blast crisis of patients with chronic myeloid leukemia. J Natl Cancer Inst 73:655–661
Wong RL, Katz ME, Ogata K, Tan EM, Cohen S (1987) Inhibition of nuclear DNA synthesis by an auto-antibody to proliferating cell nuclear antigen/cyclin. Cell Immunol 110:443–448
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Tsuji, T., Shrestha, P., Yamada, K. et al. Proliferating cell nuclear antigen in malignant and pre-malignant lesions of epithelial origin in the oral cavity and the skin: an immunohistochemical study. Vichows Archiv A Pathol Anat 420, 377–383 (1992). https://doi.org/10.1007/BF01600508
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DOI: https://doi.org/10.1007/BF01600508