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Ki-67 Expression. (A) Basal layer of an OLP lesion. (B) Germinal center of tonsillar tissue positive control
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Previously, we have shown that the telomerase RNA component hTR is highly expressed in the epithelium of non-dysplastic Oral Lichen Planus (OLP) lesions (11). We concluded that it is possible that this high expression might be related to the increased cellular proliferation seen in OLP rather than being an indicator of potential malignant transform...
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Lichen planus is an idiopathic inflammatory condition, which may involve mucosa of the oral cavity, gastrointestinal tract, larynx or the cutaneous surface either in isolation or in combinations. Mucosal lichen planus is more common than the cutaneous variant. Isolated lip involvement is very rare and should be differentiated from other similar leu...
Citations
... Therefore, a counterbalancing mechanism is expected as a response from the oral epithelium to maintain its integrity. In fact, several molecular studies indicated evidence of increased cellular turnover rate, in the form of increased cellular proliferation, in epithelial cells of oral lichen planus [21][22][23][24]. In addition, other authors have demonstrated mixed patterns of both apoptosis and increased cellular proliferation occurring simultaneously [25][26][27]. ...
Pro-inflammatory Cytokines are powerful mediators which play a central role in both innate and adapted immune responses. Aberrant productions of cytokines may lead to the onset of immune deficiency, allergy or autoimmunity, which are involved in the mechanisms of various immune-mediated inflammatory diseases. Oral lichen planus (OLP) is a chronic inflammation disease affecting the oral mucosa with unknown aetiology. Previous studies have described the abnormal expression patterns of various inflammation-related cytokines, such as IL-1, 2, 4, , 6, 8, 10, 12, 17, 18, TGF-β, IFN-γ and TNF-α, in lesions, saliva, serum and peripheral blood mononuclear cells from patients with OLP, which may reflect the immune dysregulation status and emerge as central players in the immunopathogenesis of OLP. Besides, the gene polymorphisms of several cytokines such as IFN-γ, TNF-α, IL-4, IL-10 have been found to be involved in the susceptibility of OLP. The aim of this paper is to briefly present the characteristics and a current description about the involvement of these pro-inflammatory cytokines in the pathogenesis of OLP leading to understand the eventual malignant transofrmation of OLP to Oral Cancer.
... Carcinogenesis (carcinogenesis) is a multi-step process which can occur with the advent of successive mutations and epigenetic abnormalities in multiple genes, which in the meantime, cell cycle control genes are important. Regular progress of cells during cell cycle progression is driven precisely by a protein called Cyclin, which play his role by connecting and activation of Cyclin dependent kinases (CDK) [11]. ...
... Cyclin D1 is a45 KDa protein and is coded by the gene CCNDI located on chromosome 13 q 11 [12]. During the different stages of the cell cycle (G1 S G2 M), Cyclin D1 is a part of a molecular system that plays an important role in necessary settings to pass from G1 to S (checkpoint G1/S) [11,13]. ...
... So that the protein after forming the sets of CDK4 and CDK6, leads to protein phosphorylation of retinoblastoma (RB). With phosphorylating RB, inhibiting the activity of transcription factor E 2E is removed and the cell enters the S phase [11,13,14]. ...
Oral lichen planus (OLP) is a chronic inflammatory disease with unknown etiology, and WHO has classified it as a premalignant lesions that could be transformed to oral squamous cell carcinoma (OSCC). Since uncontrolled cellular proliferation is considered the base of malignancy, the aim of this study is the comparison Cyclin D1 immunohistochemical expression in OLP and OSCC. Cyclin D1 immunohistochemical expression was evaluated in 21 samples of hyperplasia without dysplasia, (group :A), OLP (group: B) and OSCC (group: C).Label index of the Cyclin D1 expression was 13.69±6.006, 28.38±3.35 and 66.94±14.49, in A, B, and C groups respectively. Significant difference was found statistically between 3 groups (p<0.001) and between A and B (p<0.009), B and C (p<0.001), A and C (p<0.001).we have seen a statistically significant difference between groups and each 2 groups in semi-quantitative analysis. (p<0.001). The findings of this study with Cyclin D1 showed that cellular proliferation in the lesions of OLP samples is significantly lower than OSCC samples. This will be a warning to clinicians so that patients with OLP, especially those with increased cell proliferation are always followed by regular periodic examinations and detailed and continuous follow-up to detect the slightest changes in lesions in the early stages and provide appropriate treatment.
... Therefore, the observed telomerase activity in OLP may be associated with pro liferation and inflammation of the lesions. Similar results were reported by Flatharta et al 64,66 in 2008. ...
Aim:
Many studies have suggested that a lesion originally diagnosed as oral lichen planus (OLP) has different possibilities of undergoing malignant transformation in time, although these findings remain a controversial issue; for example, some studies reported different values of potential malignancy of OLP.
Introduction:
World Health Organization (WHO) classifies OLP as a "potentially malignant disorder" with unspecified malignant transformation risk, and suggests that OLP patients should be closely monitored. Numerous studies have attempted to confirm the malignant transformation potential of OLP.
Review results:
The Cochrane Controlled Trials Register, Medline and EMBASE databases, PubMed, Google Scholar, Ovid, Up To Date, BMJ Clinical Evidence, MD Consult, and Science Direct were searched for papers published between 1997 and 2015. The medical subject heading search terms were "lichen planus," "oral lichen planus," "erosive oral lichen planus," "dysplasia," "oral precancerous condition," "oral premalignant condition," oral cancer, oral squamous cell carcinoma (OSCC), and atrophic lichen planus. A total of 120 English language abstracts were reviewed, and 50 relevant articles identified. Because of the extensive literature on the association between OLP and SCC, we have divided the data into genetic and non-genetic factors for more accurate assessment.
Conclusion:
In this evidence base, malignant transformation ranges from 0 to 37% with a mean of 4.59%. The highest rate of malignancy was noted in erythematosus and erosive lesions. In this way, follow-up of OLP patients could be carried out more efficiently and appropriately.
Clinical significance:
Oral lichen planus is a premalignant lesion. All types of OLP in any site of oral mucosa must be monitored regularly.
... Recently, OLP has been proposed as an ideal model of inflammation-induced cancer (4). Several molecular studies have shown evidence of increased cellular turnover rate, in the form of increased cellular proliferation, in epithelial cells of oral lichen planus (5)(6)(7)(8). ...
Background: Oral lichen planus (OLP) is a relatively common, chronic inflammatory condition, which is considered a precancerous lesion. The Ki-67 antigen is expressed in all the phases of the cellular cycle in proliferative cells. Dierent studies have suggested the relationship between incidences of malignancy in precancerous lesions and the occurrence of this protein. Objectives: This study aimed to evaluate Ki-67 expression in erosive and non-erosive oral lichen planus. Materials and Methods: Specimens (formalin-fixed and paran-embedded) of 30 lesions of erosive OLP and 30 lesions of non- erosive OLP were referred for immunehistochemistry (IHC) analysis of Ki-67. Results of immunohistochemistry were statistically evaluated by means of the chi-square test and independent t-test. The level of statistical significance was established at P < 0.05. Results: The mean expression of Ki-67 in patients with erosive OLP was higher than people in the control group. These dierences were statistically significant (P = 0.041). Conclusions: Since Ki-67 is extensively accepted as an important biomarker in diagnosis, prognosis and treatment of cancerous and precancerous lesions, a high degree of presence of this biomarker in chronic precancerous lesions, such as erosive OLP, can be of great use in prognosis and suggested treatments.
... According to telomere hypothesis, progressive shortening of the ends of chromosomes (telomeres) in the absence of telomerase is the mitotic clock that regulates the onset of replicative senescence in normal somatic cells [54]. Telomerase activity is undetectable in normal somatic cells, however can be evaluated in biopsied tissue from oral cancer [61]. Telomerase activity is used as a marker in the diagnosis of pre-neoplasic or neoplasic oral mucosa lesions, as 80-90% of such tumors have high levels of telomeric expression, particularly of the hTERT sub-unit [62]. ...
Cancer is a class of diseases characterized by uncontrolled cell growth. The development of cancer takes place in a multi-step process during which cells acquires a series of mutations that eventually lead to unrestrained cell growth and division, inhibition of cell differentiation, and evasion of cell death. Dysregulation of oncoapoptotic genes, growth factors, receptors and their downstream signaling pathway components represent a central driving force in tumor development. The detailed studies of signal transduction pathways for mechanisms of cell growth and apoptosis have significantly advanced our understanding of human cancers, subsequently leading to more effective treatments. Oral squamous cell carcinoma represents a classic example of multi-stage carcinogenesis. It gradually evolves through transitional precursor lesions from normal epithelium to a full-blown metastatic phenotype. Genetic alterations in many genes encoding crucial proteins, which regulate cell proliferation, differentiation, survival and apoptosis, have been implicated in oral cancer. As like other solid tumors, in oral cancer these genes include the ones coding for cell cycle regulators or oncoproteins (e.g. Ras, Myc, cyclins, CDKs, and CKIs), tumor suppressors (e.g. p53 and pRb), pro-survival proteins (e.g. telomerase, growth factors or their receptors), anti-apoptotic proteins (e.g. Bcl2 family, IAPs, and NF-kB), pro-apoptotic proteins (e.g. Bax and BH-3 family, Fas, TNF-R, and caspases), and the genes encoding key transcription factors or elements for signal transduction leading to cell growth and apoptosis. Here we discuss the current knowledge of oncoapoptotic regulation in human cancers with special reference to oral cancers.
... Therefore, a counterbalancing mechanism is expected as a response from the oral epithelium to maintain its integrity. In fact, several molecular studies indicated evidence of increased cellular turnover rate, in the form of increased cellular proliferation, in epithelial cells of oral lichen planus [21][22][23][24]. In addition, other authors have demonstrated mixed patterns of both apoptosis and increased cellular proliferation occurring simultaneously [25][26][27]. ...
Oral lichen planus (OLP) is a chronic oral inflammatory disease of unknown etiology. According to reports, 1-2% of OLP patients develop oral squamous cell carcinoma (OSCC) in the long run. While World Health Organization (WHO) classifies OLP as "a potentially malignant disorder," it is still a matter of debate which mechanisms drive OLP to such a condition. The current hypothesis connecting OLP and OSCC is that chronic inflammation results in crucial DNA damage which over time results in cancer development. Initial studies investigating the OLP and OSCC link were mainly retrospective clinical studies. Over the past years, several amount of information has accumulated, mainly from molecular studies on the OLP malignant potential. This article is a critical review of whether OLP has a malignant potential and, therefore, represents a model of preneoplastic inflammation.
... Telomerase is made up of three major parts namely, human telomerase reverse transcriptase (hTERT) 12 , human telomerase RNA (hTR) 13 and telomeraseassociated protein 1 (TP1) and telomerase-associated protein 2 14 . Among these only the expression of hTERT has been shown to correlate closely with telomerase activity. ...
Pancreatic cancer has one of the worst prognoses among all types of cancers. The survival rate is less than 5 per cent; this is due to difficulty in diagnosing at an early stage. Despite the improvements in diagnostic imaging techniques such as computed tomography, magnetic resonance imaging, etc., the early diagnosis of pancreatic cancer is still difficult. Alternative methods of diagnosing pancreatic cancer at an early stage are presently been explored. The detection of telomerase activity has been proposed to be a useful tool in the diagnosis of pancreatic cancer. Telomerase is made up of three major parts namely, human telomerase reverse transcriptase, human telomerase and telomerase -associated protein. Several researchers have shown telomerase activity in tissues and fluids of patients with pancreatic and other types of cancers. About 95 per cent telomerase activity has been detected in pancreatic adenocarcinoma. Since telomerase activity is present in a vast majority of human cancers, it might have a role in the diagnosis and treatment of cancer.
