Immunostaining for Proliferating Cell Nuclear Antigen: Its Role in Determination of Proliferation in Routinely Processed Human Brain Tumor Specimens

Overview

Journal Acta Neuropathol

Specialty Neurology

Date 1993 Jan 1

PMID 7906072

Citations 12

Authors

S Khoshyomn

H Maier

T Morimura

K Kitz

H Budka

Affiliations

Soon will be listed here.

Abstract

Alcohol- and formalin-fixed, paraffin-embedded samples of 71 brain tumors (35 gliomas, 22 metastatic carcinomas, 8 meningiomas and 6 other tumors) were investigated by immunocytochemistry with three different monoclonal antibodies against proliferating cell nuclear antigen (PCNA)/cyclin (19A2; 19F4; PC10). PC10 was found to work best; it is applicable to both alcohol- and formalin-fixed tumor samples. PCNA labeling indices (LIs) were compared in the same tumors with LIs obtained by Ki-67 immunostaining of frozen sections and by in vitro incubation with bromodeoxyuridine (BrdUrd); in the latter preparations, BrdUrd LIs could be compared with PCNA LIs in the very same areas of serial sections. In gliomas, PCNA LIs were 0.7-80.2% (mean 31.7%), in metastases 0-76.0% (mean 47.8%), and in meningiomas 0-53.0% (mean 19.3%). In general, PCNA LIs were highly significantly correlated with Ki-67 LIs (P = 0.0002) and BrdUrd LIs (P = 0.0001). However, when tumor subgroups are considered, only gliomas show a significant correlation with Ki-67 and BrdUrd LIs. Despite this statistical correlation, PCNA expression was out of proportion to proliferation indices as determined by both other methods in almost one third of all brain tumors. Immunocytochemistry for PCNA produces a broad spectrum of staining intensity of labeled nuclei, whose number is dependent upon the sensitivity of the immunocytochemical technique used. Thus, inter-observer and inter-laboratory variabilities in PCNA LI determination may occur. Overlapping of PCNA LIs between tumor subgroups of varying malignancy further limits the informational value for the individual case.(ABSTRACT TRUNCATED AT 250 WORDS)

Citing Articles

CENPA acts as a prognostic factor that relates to immune infiltrates in gliomas.

Wang B, Wei W, Long S, Wang L, Yang B, Wu D Front Neurol. 2022; 13:1015221.

PMID: 36341103 PMC: 9626989. DOI: 10.3389/fneur.2022.1015221.

Determination of key aspects of precursor cell proliferation, cell cycle length and kinetics in the adult mouse subgranular zone.

Mandyam C, Harburg G, Eisch A Neuroscience. 2007; 146(1):108-22.

PMID: 17307295 PMC: 2230096. DOI: 10.1016/j.neuroscience.2006.12.064.

Techniques to assess the proliferative potential of brain tumors.

Quinones-Hinojosa A, Sanai N, Smith J, McDermott M J Neurooncol. 2005; 74(1):19-30.

PMID: 16078103 DOI: 10.1007/s11060-004-5758-0.

Proliferative activity as measured by MIB-1 labeling index and long-term outcome of cerebellar juvenile pilocytic astrocytomas.

Roessler K, Bertalanffy A, Jezan H, Slavc I, Czech T, Budka H J Neurooncol. 2002; 58(2):141-6.

PMID: 12164686 DOI: 10.1023/a:1016053229688.

Immunohistochemical detection of cell growth fraction in formalin-fixed and paraffin-embedded murine tissue.

Birner P, Ritzi M, Musahl C, Knippers R, Gerdes J, Voigtlander T Am J Pathol. 2001; 158(6):1991-6.

PMID: 11395376 PMC: 1891991. DOI: 10.1016/S0002-9440(10)64670-6.

References

Benjamin D, Gown A . Aberrant cytoplasmic expression of proliferating cell nuclear antigen in Hodgkin's disease. Am J Surg Pathol. 1991; 15(8):764-8. DOI: 10.1097/00000478-199108000-00006. View

Hsu S, RAINE L, FANGER H . Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981; 29(4):577-80. DOI: 10.1177/29.4.6166661. View

Bauer G, Burgers P . The yeast analog of mammalian cyclin/proliferating-cell nuclear antigen interacts with mammalian DNA polymerase delta. Proc Natl Acad Sci U S A. 1988; 85(20):7506-10. PMC: 282220. DOI: 10.1073/pnas.85.20.7506. View

Dervan P, Magee H, Buckley C, Carney D . Proliferating cell nuclear antigen counts in formalin-fixed paraffin-embedded tissue correlate with Ki-67 in fresh tissue. Am J Clin Pathol. 1992; 97(5 Suppl 1):S21-8. View

Louis D, Edgerton S, Thor A, Hedley-Whyte E . Proliferating cell nuclear antigen and Ki-67 immunohistochemistry in brain tumors: a comparative study. Acta Neuropathol. 1991; 81(6):675-9. DOI: 10.1007/BF00296379. View

Robbins B, de la Vega D, Ogata K, Tan E, Nakamura R . Immunohistochemical detection of proliferating cell nuclear antigen in solid human malignancies. Arch Pathol Lab Med. 1987; 111(9):841-5. View

Maier H, Ofner D, HITTMAIR A, Kitz K, Budka H . Classic, atypical, and anaplastic meningioma: three histopathological subtypes of clinical relevance. J Neurosurg. 1992; 77(4):616-23. DOI: 10.3171/jns.1992.77.4.0616. View

Bravo R, Frank R, Blundell P . Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature. 1987; 326(6112):515-7. DOI: 10.1038/326515a0. View

Galand P, Degraef C . 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 Tissue Kinet. 1989; 22(5):383-92. DOI: 10.1111/j.1365-2184.1989.tb00223.x. View

10.

Tan C, Sullivan K, Li X, Tan E, Downey K, So A . Autoantibody to the proliferating cell nuclear antigen neutralizes the activity of the auxiliary protein for DNA polymerase delta. Nucleic Acids Res. 1987; 15(22):9299-308. PMC: 306469. DOI: 10.1093/nar/15.22.9299. View

11.

Bravo R . Existence of two populations of cyclin/proliferating cell nuclear antigen during the cell cycle: association with DNA replication sites. J Cell Biol. 1987; 105(4):1549-54. PMC: 2114668. DOI: 10.1083/jcb.105.4.1549. View

12.

Mathews M, Bernstein R, Franza Jr B, Garrels J . Identity of the proliferating cell nuclear antigen and cyclin. Nature. 1984; 309(5966):374-6. DOI: 10.1038/309374a0. View

13.

Morris G, Mathews M . Regulation of proliferating cell nuclear antigen during the cell cycle. J Biol Chem. 1989; 264(23):13856-64. View

14.

Prelich G, Kostura M, Marshak D, Mathews M, Stillman B . The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro. Nature. 1987; 326(6112):471-5. DOI: 10.1038/326471a0. View

15.

Ogata K, Kurki P, Celis J, Nakamura R, Tan E . Monoclonal antibodies to a nuclear protein (PCNA/cyclin) associated with DNA replication. Exp Cell Res. 1987; 168(2):475-86. DOI: 10.1016/0014-4827(87)90020-6. View

16.

Waseem N, Lane D . Monoclonal antibody analysis of the proliferating cell nuclear antigen (PCNA). Structural conservation and the detection of a nucleolar form. J Cell Sci. 1990; 96 ( Pt 1):121-9. DOI: 10.1242/jcs.96.1.121. View

17.

Maier H, Morimura T, Ofner D, Hallbrucker C, Kitz K, Budka H . Argyrophilic nucleolar organizer region proteins (Ag-NORs) in human brain tumors: relations with grade of malignancy and proliferation indices. Acta Neuropathol. 1990; 80(2):156-62. DOI: 10.1007/BF00308919. View

18.

Garcia R, Coltrera M, Gown A . Analysis of proliferative grade using anti-PCNA/cyclin monoclonal antibodies in fixed, embedded tissues. Comparison with flow cytometric analysis. Am J Pathol. 1989; 134(4):733-9. PMC: 1879787. View

19.

Morimura T, Kitz K, STEIN H, Budka H . Determination of proliferative activities in human brain tumor specimens: a comparison of three methods. J Neurooncol. 1991; 10(1):1-11. DOI: 10.1007/BF00151242. View

20.

Prelich G, Tan C, Kostura M, Mathews M, So A, Downey K . Functional identity of proliferating cell nuclear antigen and a DNA polymerase-delta auxiliary protein. Nature. 1987; 326(6112):517-20. DOI: 10.1038/326517a0. View