Cell proliferation activity and the expression of cell cycle regulatory proteins in oral lichen planus

Hirota, Makoto; Ito, Takaaki; Okihara, Koji; Kawabe, Ryoichi; Yazawa, Takuya; Hayashi, Hiroyuki; Nakatani, Yukio; Fujita, Kiyohide; Kitamura, Hitoshi

doi:10.1034/j.1600-0714.2002.310403.x

Cited by 54 publications

(57 citation statements)

References 32 publications

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“…Due to ethical considerations and lack of normal tissue blocks the control group in the present study consisted of epithelial hyperplasia with no dysplasia. It is considerable that result of comparison between groups A and B in this study was similar to other studies in which OLP have been compared to normal mucosa regardless of the evaluation methods and cell proliferation markers applied (Tipoe et al, 1996;Hirota et al, 2002;Taniguchi et al, 2002;Lee et al, 2005;González Moles et al, 2009;HadziMihailovic et al, 2012). In contrast, Bloor et al (1999) reported no difference for Ki67 expression between the OLP and normal mucosa (Bloor et al, 1999).…”

Section: Discussionsupporting

confidence: 85%

“…The injured cells in OLP target some complex molecular mechanisms in order to arrest cell cycle (to repair their damaged DNA and maintain genomic stability) or in order to activate apoptosis pathway (to eliminate cells with severity damaged DNA) (Hirota et al, 2002;Taniguchi et al, 2002;Bascones-Ilundain et al, 2008;Liu et al, 2010;Georgakopoulou et al, 2012). In addition, these injured cells can enter cell cycle and proliferate (Liu et al, 2010;Georgakopoulou et al, 2012) Although mechanisms involved in an increase in proliferation are still unknown (Hirota et al, 2002), one of the mechanisms might be related to the release of cytokines and inflammatory mediators from injured keratinocytes or inflammatory cells in OLP (da Silva Fonseca and do Carmo, 2001;Liu et al, 2010;Mattila et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, these injured cells can enter cell cycle and proliferate (Liu et al, 2010;Georgakopoulou et al, 2012) Although mechanisms involved in an increase in proliferation are still unknown (Hirota et al, 2002), one of the mechanisms might be related to the release of cytokines and inflammatory mediators from injured keratinocytes or inflammatory cells in OLP (da Silva Fonseca and do Carmo, 2001;Liu et al, 2010;Mattila et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

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Suitability/Unsuitability of Cell Proliferation as an Indicator of Malignant Potential in Oral Lichen Planus: an Immunohistochemical Study

Zargaran

Jamshidi²,

Eshghyar³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Oral lichen planus (OLP) is categorized as premalignant lesion although its malignant potential is a matter of controversy. The objective of this study was to investigate Ki67 expression in OLP, oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). Materials and Methods: Expression of Ki67 was evaluated through immunohistochemistry (IHC) in groups of A (17 cases of epithelial hyperplasia), B (16 cases of OLP), C1 (10 cases of mild epithelial dysplasia), C2 (10 cases of severe epithelial dysplasia), D1 (10 cases of well-differentiated OSCC), and D2 (10 cases of poorly-differentiated OSCC). Results: There was a significant difference in Ki67 expression based on quantitative analysis among the six studied groups as well as group B compared bilaterally with groups C2, D1 and D2 (p< 0.0001). However, there was no significant difference between groups B and C1 or between groups D1 and D2 (p> 0.05). Conclusions: Based on the results of the present study it may not be possible to definitely consider malignant transformation potential for OLP. However, expression of Ki67 was significantly higher in OLP than that of epithelial hyperplasia with no significant difference from that of mild epithelial dysplasia. This should be considered by clinicians to carefully and regularly follow up OLP lesions to detect potential subtle changes at an early stage.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Suitability/Unsuitability of Cell Proliferation as an Indicator of Malignant Potential in Oral Lichen Planus: an Immunohistochemical Study

Zargaran

Jamshidi²,

Eshghyar³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…In contrast, markers of cellcycle arrest, such as p27, may be expected to increase in the presence of these drugs (Malik et al, 2003). Apoptosis, which could also conceivably increase with certain interventions, is such a rare event in the normal buccal mucosa that its usefulness as a potential PD marker is uncertain (Hirota et al, 2002;Loro et al, 2002;Hague et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…The choice of normal tissue for a given drug study is likely to depend on a number of different factors, including the level and variability of expression of the biomarker of interest. Literature reports suggest that the buccal mucosa has a high baseline proliferation index (Jordan et al, 1998;Hirota et al, 2002;Kurokawa et al, 2003), making it a potentially attractive tissue for assessing antiproliferative end points. Unfortunately, these indices are often obtained from individuals undergoing follow up for various oral pathologies, therefore field effects skewing these 'normal' values cannot be ruled out.…”

mentioning

confidence: 99%

Assessing proliferation, cell-cycle arrest and apoptotic end points in human buccal punch biopsies for use as pharmacodynamic biomarkers in drug development

et al. 2005

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Easily accessible normal tissues expressing the same molecular site(s) of drug action as malignant tissue offer an enhanced potential for early proof of anticancer drug mechanism and estimation of the biologically effective dose. Studies were undertaken in healthy male volunteers to assess the tolerability of single and multiple (four in 24 h) 3 mm punch biopsies of the buccal mucosa, and to determine the feasibility of detecting and quantifying a range of proliferation, cell-cycle arrest and apoptosis markers by immunohistochemistry (IHC) for use as potential pharmacodynamic (PD) end points. The biopsy procedure was well tolerated with 100% of volunteers stating that they would undergo single (n ¼ 10) and multiple (n ¼ 12) biopsies again. Total retinoblastoma protein (pRb), phosphorylated pRb (phospho-pRb), total p27, phosphorylated p27 (phospho-p27), phosphorylated-histone H3 (phospho-HH3), p21, p53, Cyclin A, Cyclin E, Ki67 all produced good signal detection, but M30, cleaved caspase 3 and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling did not. Total pRb, phospho-pRb, total p27 and phospho-p27 were quantified further in a multiple biopsy study to allow components of variability to be addressed to inform future sizing decisions on intervention studies. Neither site of biopsy within the oral cavity, nor the nominal time of biopsy had any significant impact on any of the four markers expression levels. Inter-and intrasubject coefficients of variation (CVs) that could be used to size future intervention studies for pRb, phospho-pRb, total p27 and phospho-p27 were 14, 19, 18 and 16%; and 18, 29, 25 and 19%, respectively. In conclusion, quantitation of such markers in 3 mm buccal punch biopsies would be suitable to explore as PD end points within intervention studies of drugs acting on these pathways.

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Pharmacodynamic Studies in Early Phase Drug Development

Camidge

Jimeno²

2010

Principles of Anticancer Drug Development

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Cell proliferation activity and the expression of cell cycle regulatory proteins in oral lichen planus

Abstract: These complex changes, which concomitantly occur in the injured mucosal epithelium, could contribute to the development and maintenance of characteristic mucosal epithelial architectures seen in OLP.

Cited by 54 publications

References 32 publications

Suitability/Unsuitability of Cell Proliferation as an Indicator of Malignant Potential in Oral Lichen Planus: an Immunohistochemical Study

Suitability/Unsuitability of Cell Proliferation as an Indicator of Malignant Potential in Oral Lichen Planus: an Immunohistochemical Study

Assessing proliferation, cell-cycle arrest and apoptotic end points in human buccal punch biopsies for use as pharmacodynamic biomarkers in drug development

Pharmacodynamic Studies in Early Phase Drug Development

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