Immunohistochemical markers of cellular proliferation: achievements, problems and prospects

Hall, Peter A.; Woods, Amanda L.

doi:10.1111/j.1365-2184.1990.tb01343.x

Cited by 110 publications

(92 citation statements)

References 137 publications

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“…Most of the correlations have yielded good results with few exceptions (7,23,24). Further investigation is warranted to understand if the discrepancies noted in the exceptions are related to PCNA gene regulation, PCNA expression in different cell types, and/or differences in the antigenicity of anti-PCNA antibodies (25).…”

Section: Resultsmentioning

confidence: 99%

Comparison of Proliferating Cell Nuclear Antigen to Tritiated Thymidine As a Marker of Proliferating Hepatocytes in Rats

Foley¹,

Ton²,

Maronpot³

et al. 1993

Environmental Health Perspectives

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Proliferating cell nuclear antigen (PCNA), an endogenous nuclear protein, has recently been used to identify replicating cells. PCNA was compared to tritiated thymidine ([3Hl-TdR), a reliable and accurate exogenous labeling agent, to ascertain if PCNA gives comparable results for quantitative cell proliferation. Male F344 rats were treated with a single dose of 500 mg/kg 4-acetylaminofluorene (4-AAF), a known liver mitogen. Rats (n = 5) were euthanized and necropsied at 6, 12, 18, 24, 36, 48, 96, or 192 hr after treatment. Two hours before necropsy, rats were pulse-dosed with [3H]-TdR (2 mCi/kg body weight). Livers were sectioned, autoradiography performed, and labeling indexes (LI), a measurement of the percentage of S-phase hepatocytes, determined. One and a half years after the completion of this study, the archival paraffin blocks of the liver tissue were sectioned and stained for PCNA by an immunohistochemical procedure. Immunocytochemical staining patterns of proliferating cell nuclear antigen expression

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Section: Resultsmentioning

confidence: 99%

Comparison of Proliferating Cell Nuclear Antigen to Tritiated Thymidine As a Marker of Proliferating Hepatocytes in Rats

Foley¹,

Ton²,

Maronpot³

et al. 1993

Environmental Health Perspectives

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“…Determination of S-phase cells is even more complicated in tumors, which do not deviate in terms of DNA-content from benign cells (26,27). Instead of measuring DNA-synthesis itself by the incorporation of DNA precursors, markers related to DNA synthesizing (proliferating) cells have been used to histochemically stain tissue sections, i.e Ki-67 and PCNA (proliferating cell nuclear antigen) (28,29).…”

Section: Discussionmentioning

confidence: 99%

Thymidine kinase 1: A proliferation marker for determining prognosis and monitoring the surgical outcome of primary bladder carcinoma patients

Zhang

Quan-an²,

Zou³

et al. 2006

Oncol Rep

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Abstract. Reliable markers for monitoring bladder tumor therapy are needed to evaluate treatment effectiveness. Thymidine kinase 1 (TK1) is an enzyme involved in DNA synthesis and therefore proliferation-dependent. Serum concentration of TK1 (STK1) correlates with malignancy in various types of cancer, thus reflecting treatment results. This study explores for the first time the use of STK1 concentration, both as a prognostic marker and to monitor the outcome of bladder carcinoma surgery. STK1 in 56 bladder carcinoma patients was measured pre-operatively, and postoperatively at 1 week and 1, 3, and 6 months, using an immune ECL dot blot assay. An anti-TK1 chicken IgY antibody was used to determine STK1 concentrations. Mean pre-operative STK1 of bladder carcinoma patients was significantly higher than that of healthy individuals, with no overlap of individual values. STK1 concentrations increased significantly with tumor stage (I-III) and T-values (T1-T2), but not tumor grade (G1-G4). STK1 gradually declined, being 66% lower after 1 week. STK1 reached the level of healthy controls at 1 month and remained there for at least 6 months, post-operatively until this study ended. Since STK1 concentration correlates with tumor stage, degree of invasion and metastasis, and monitors the surgical outcome, it can be a reliable index to diagnose and determine prognosis in post-operative bladder carcinoma.

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“…PCNA, which is synthesized in early G 1 phase of the cell cycle, is an auxillary protein to d and 1 DNA polymerases during the S phase in cycling cells, and its immunoreactivity has a linear relationship with thymidine incorporation in a wide range of normal tissues (Hall & Woods 1990). The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nickend-labelling (TUNEL) assay is now almost considered a classic apoptosis assay, in which the free 3 0 -OH ends of double-stranded DNA fragments that are formed preferentially in apoptotic cells are labelled (Gavrieli et al 1992).…”

Section: Introductionmentioning

confidence: 99%

“…Proliferating cell nuclear antigen (PCNA) is used widely to provide an immunohistochemical assessment of cellcycle activity in normal tissues (Hall & Woods 1990), and its expression is used as a marker of cell proliferation in cultured granulosa cells (the female equivalent of Sertoli cells) following their stimulation with follicle-stimulating hormone (FSH) and activin (El-Hefnawy & Zeleznik 2001). PCNA, which is synthesized in early G 1 phase of the cell cycle, is an auxillary protein to d and 1 DNA polymerases during the S phase in cycling cells, and its immunoreactivity has a linear relationship with thymidine incorporation in a wide range of normal tissues (Hall & Woods 1990).…”

Section: Introductionmentioning

confidence: 99%

Stage and season effects on cell cycle and apoptotic activities of germ cells and Sertoli cells during spermatogenesis in the spiny dogfish (Squalus acanthias)

McClusky¹

2005

Reproduction

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To understand the processes involved in the spatial and temporal maturation of testicular cells in Squalus acanthias, we used standard morphometry, proliferating-cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) immunohistochemistry. Except for immature spermatocysts (germinal zone, GZ; early-stage premeiotic, E-PrM), the number of cysts in all subsequent stages and the total number of cysts in the spermatogenic progression varied seasonally. The spermatogenic cycle spans about 2 years and is interrupted by germcell clone deletion via apoptosis at the mitosis-meiosis transition in April/May, manifesting as a zone of degeneration (ZD). Rate of displacement of the ZD across the testis diameter indicates that late-stage premeiotic (L-PrM) generations 12-13 require 9 -10 months to reach the mature-spermatid stage. Also, the number of cysts completing spermatogenesis is approximately 4-5-fold less than the number that entered spermatogenesis proper 2 years earlier. Pronounced gonocytogenesis in the germinal ridge was coincident with ZD formation in April/May, but it was absent in the fall when mature spermatogonial and meiotic activities had resumed. Whereas strong Sertoli cell PCNA immunoreactivity dominated the GZ cyst cell-cycle activities throughout the year, except during the spring/summer months, the spermatogonial-and Sertoli-cell PCNA indices in E-PrM cysts were inversely related. PCNA immunoreactivity in spermatocytes was seasonal and dependent on the stage of meiosis. TUNEL labelling was limited to spermatogonia and increased stage-dependently in the PrM region (L-PrM 5 mid-stage PrM @ E-PrM @ GZ), correlating with ZD formation, in a season-dependent manner. Results imply that effects of normal regulatory factors in Squalus are stage-and process-specific.

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Immunohistochemical markers of cellular proliferation: achievements, problems and prospects

Cited by 110 publications

References 137 publications

Comparison of Proliferating Cell Nuclear Antigen to Tritiated Thymidine As a Marker of Proliferating Hepatocytes in Rats

Comparison of Proliferating Cell Nuclear Antigen to Tritiated Thymidine As a Marker of Proliferating Hepatocytes in Rats

Thymidine kinase 1: A proliferation marker for determining prognosis and monitoring the surgical outcome of primary bladder carcinoma patients

Stage and season effects on cell cycle and apoptotic activities of germ cells and Sertoli cells during spermatogenesis in the spiny dogfish (Squalus acanthias)

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