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[Expressions of PDCD5 and p53 in oral leukoplakia and oral squamous cell carcinoma].

OBJECTIVE: To study the relationship of the expressions of new apoptosis-related gene PDCD5 and p53 in oral normal mucosa, oral leukoplakia and oral squamous cell carcinoma. METHODS: The expressions of PDCD5 and p53 were observed separately in 17 samples of oral normal mucosa, 60 of oral leukoplakia, and 30 of oral squamous cell carcinoma by Immunohistochemical means. RESULTS: PDCD5 positive rate in oral normal mucosa was 88.2%, in oral leukoplakia was 63.3%, and in oral squamous cell carcinoma was 30%. P53 positive rate in oral normal mucosa was 0, in oral leukoplakia was 31.7%, and in oral squamous cell carcinoma was 60%. There was a negative relationship between PDCD5 SII and P53 SII in every lesion. CONCLUSION: It suggests that both PDCD5 and p53 could be used as molecular markers of carcinogenesis for oral epithelium.

Adult↗

Systematic review of randomized trials for the treatment of oral leukoplakia.

Oral leukoplakia is a relatively common oral lesion that, in a varying proportion of cases, undergoes malignant transformation. The aim of this review was to assess the effectiveness of treatments for leukoplakia. Randomized controlled trials (RCTs) enrolling patients with a diagnosis of oral leukoplakia were identified by searching biomedical databases, hand-searching relevant oral medicine journals, and contacting oral medicine experts through a European mailing list. The methodological quality of included studies was assessed on the basis of the method of allocation concealment, blindness of the study, and loss of participants. Data were analyzed by calculating relative risk. Malignant transformation of leukoplakia, demonstrated by histopathological examination, was the main outcome considered. Secondary outcomes included clinical resolution of the lesion and variation in dysplasia severity. Six RCTs were included in the review. Vitamin A and retinoids were tested in four RCTs; the other agents tested were bleomycin, mixed tea, and beta carotene. Malignant transformation was recorded in just two studies: none of the treatments tested showed a benefit when compared with placebo. Treatment with beta carotene and vitamin A or retinoids was associated with better rates of clinical remission, compared with placebo or absence of treatment. Whenever reported, a high rate of relapse was a common finding. Side effects of variable severity were often described; however, interventions were well accepted by patients since drop-out rates were similar between treatment and control groups. It is noteworthy that the possible effectiveness of surgical interventions, including laser therapy and cryotherapy, has apparently never been studied by means of an RCT. To date, in conclusion, there is no evidence of effective treatment in preventing malignant transformation of leukoplakia. Treatments may be effective in the resolution of lesion; however, relapses and adverse effects are common.

Antineoplastic Agents↗

Carbon dioxide laser surgery of oral leukoplakia.

Oral leukoplakia is a precancerous lesion of the oral mucosa. The risk of malignant transformation depends on the clinical and histologic classification and the location of the lesion. For a nonhomogeneous leukoplakia, this risk is 23.4% to 38.0%. In the presence of epithelial dysplasia, the possibility of malignant transformation is 36.3% to 43.0%. Leukoplakia is limited to the epithelium, so a selective removal of this part of the mucosa seems to be the best preventive treatment. Carbon dioxide laser surgery accomplishes a superficial removal by evaporation. A total of 70 patients with 103 oral leukoplakias were treated with carbon dioxide laser evaporation. This resulted in an excellent wound healing with virtually no scarring. The patients were followed up during a period of up to 12 years (mean 5.3 years), showing a cure rate of 90%.

Adult↗

Influence of cigarette, pipe, and cigar smoking, removable partial dentures, and age on oral leukoplakia.

Oral leukoplakia, a potentially malignant lesion, has been associated with tobacco smoking, but few studies have investigated the influence of different products on lesion prevalence. In the current study 925 healthy male subjects from the Veterans Administration Dental Longitudinal Study were examined for lesion site and prevalence. The participants were grouped according to smoking status: nonsmokers, smokers of cigarettes, cigars, a pipe, cigars plus a pipe, or cigarettes plus another tobacco product. In addition, the amount of product smoked, presence of a removable partial denture, and age were examined to determine their relation to leukoplakia prevalence. The data indicated that cigar smokers had significantly fewer lesions than the other smoker groups and that persons smoking a pipe or a pipe plus cigars had the highest prevalence. Heavy cigarette smokers had significantly more palatal lesions than light to moderate cigarette smokers. While removable partial dentures did not appear to affect lesion prevalence significantly, older smokers, persons of 50 years and above, had a significantly higher prevalence than persons less than 50 years of age.

Adult↗

DNA cytometry of oral leukoplakia and oral lichen planus.

BACKGROUND: DNA cytometry is a technique that allows densitometric analysis of nuclear DNA of cells and in this way the evaluation of DNA ploidy. OBJECTIVE: The purpose of the present study was the evaluation of DNA ploidy in oral leukoplakia and oral lichen planus and correlation with histological dysplasia. METHODS: We analyzed oral incisional biopsies from a group of 40 patients with oral leukoplakias (20 homogeneous and 20 non-homogeneous) and 45 patients with oral lichen planus (25 erosive, 20 reticular), by DNA cytomorphometry, after conventional histological examination of sections stained with haematoxylin and eosin. RESULTS AND CONCLUSIONS: Eight of 20 non-homogeneous leukoplakias showed aneuploidy; (3 showed mild aneuploidy) and only 2 specimens of erosive lichen planus showed moderate aneuploidy, while all 20 cases of reticular lichen planus were diploid. There was not concordance between DNA ploidy and the degree of histological assessed dysplasia.

Aneuploidy↗

Yeast organisms associated with human oral leukoplakia.

Oral leukoplakia is a lesion of variable clinical behaviour and a malignant transformation rate of 3-6%. Leukoplakia exhibits various histologic features, hyperkeratinization being the most consistent. As yeast organisms have been encountered in a high proportion of leukoplakia cases, a causal role has been suggested for these organisms. Candida albicans is by far the most commonly isolated yeast from leukoplakia, but also other Candida species as well as Torulopsis and Saccharomyces species may be encountered. The species composition of the mycoflora in leukoplakia does however not differ from that of normal oral mucosa. Subspecies differentiation of C. albicans has revealed the existence of different oral strains between individuals and further, strain differences of C. albicans in leukoplakia and in normal mucosa have been observed. This procedure may lead to isolation and identification of the yeast organisms causally associated with leukoplakia.

Candida↗

The precancer risk of betel quid chewing, tobacco use and alcohol consumption in oral leukoplakia and oral submucous fibrosis in southern Taiwan.

In areas where the practise of betel quid chewing is widespread and the chewers also often smoke and drink alcohol, the relation between oral precancerous lesion and condition to the three habits is probably complex. To explore such association and their attributable effect on oral leukoplakia (OL) and oral submucous fibrosis (OSF), a gender-age-matched case-control study was conducted at Kaohsiung, southern Taiwan. This study included 219 patients with newly diagnosed and histologically confirmed OL or OSF, and 876 randomly selected community controls. All information was collected by a structured questionnaire through in-person interviews. A preponderance of younger patients had OSF, while a predominance of older patients had OL. Betel quid chewing was strongly associated with both these oral diseases, the attributable fraction of OL being 73.2% and of OSF 85.4%. While the heterogeneity in risk for areca nut chewing across the two diseases was not apparent, betel quid chewing patients with OSF experienced a higher risk at each exposure level of chewing duration, quantity and cumulative measure than those who had OL. Alcohol intake did not appear to be a risk factor. However, cigarette smoking had a significant contribution to the risk of OL, and modified the effect of chewing based on an additive interaction model. For the two oral premalignant diseases combined, 86.5% was attributable to chewing and smoking. Our results suggested that, although betel quid chewing was a major cause for both OL and OSF, its effect might be difference between the two diseases. Cigarette smoking has a modifying effect in the development of oral leukoplakia.

Adult↗

Evaluation of TGF-alpha and EGFR expression in oral leukoplakia and oral submucous fibrosis by quantitative immunohistochemistry.

OBJECTIVE: Oral leukoplakia (OL) and oral submucous fibrosis (OSMF) are clinically distinct preneoplastic states that precede the development of oral squamous cell carcinoma. Recently, attempts are being made to identify specific molecular event(s) as prognostic markers to identify oral precancerous lesions with higher malignant potential. The goal of the present study was to evaluate the expression of EGFR and its ligand TGF-alpha in OL with dysplasia and OSMF as intermediate markers of malignancy by quantitative immunohistochemistry. METHODS: Oral tissues were stained with monoclonal antibodies to TGF-alpha and EGFR. The results were analyzed with Photoquant image analysis software. RESULTS: The expression of TGF-alpha and EGFR was upregulated in OL, OSMF and oral squamous cell carcinomas relative to normal oral mucosa. The area and intensity of staining of TGF-alpha in the proliferative layers (stratum germinativum) increased linearly in OL with mild, moderate and severe dysplasia as compared to control mucosa (p < 0.05). EGFR levels increased linearly in the stratum spinosum in OL with increasing degrees of dysplasia (p < 0.05). In general, the expression of both proteins in OSMF was similar to that in OL with moderate dysplasia. CONCLUSIONS: EGFR and TGF-alpha represent early markers of malignancy in OL with dysplasia. Quantitative measurement of these proteins may provide intermediate endpoints in prospective chemopreventive trials.

Age of Onset↗

p53 mutation and detection of p53 protein expression in oral leukoplakia and oral squamous cell carcinoma.

In many studies the detection of p53 protein by immunohistochemistry (IHC) with one antibody is assumed to be consistent with a mutation of the gene. To determine the correlation of protein detection by immunohistochemistry and gene mutation, paraffin embedded specimens of 60 oral leukoplakias (OL) and 73 oral squamous cell carcinomas (OSCC) were analysed by IHC with two different antibodies (Do7; Pab 1801), PCR-SSCP and sequencing. In 98% of OLs and 94% of OSSCs p53 protein expression was detected with at least one antibody. Only 49% of all tissue specimen were positive with both antibodies. Molecular analysis of the same specimen showed mutations of the p53 gene in 13.3% of OLs and 9, 6% of OSCCs. p53 protein expression was not detected by IHC in 3 out of 7 OSCC with p53 mutations. According to these results detection of p53 expression by IHC is not always correlated with p53 gene mutation and failure to detect p53 protein by IHC does not prove the absence of mutation of the gene in the carcinogenesis in the oral mucosa.

Antibodies, Monoclonal↗

Ultrastructural variations and assessment of malignant transformation risk in oral leukoplakia.

Oral cancer is the most common malignancy in India, having a well defined precancerous state, leukoplakia. Various follow-up studies have shown that only 4 to 18% of oral leukoplakia lesions subsequently progress into invasive malignancy over a period of time. This study evaluates the potential of electron microscopy in the early detection of malignant changes in leukoplakia. The study revealed that of the 25 leukoplakia lesions examined, 7 showed changes akin to malignancy. Predominant ultrastructural alterations observed were reduplication and discontinuity of the basal lamina, basal cells with pleomorphic and bizarre nuclei containing perichromatin and interchromatin granules, prominent intercellular spaces and poorly formed desmosomes. Since none of these changes were evident under light microscopy the study demonstrates the value of electron microscopy in evaluating oral carcinogenesis. A long term follow-up of such patients is needed to understand the prognostic implications of these ultrastructural variation and how they can be used as a base line for better light microscopic evaluation.

Cell Transformation, Neoplastic↗

[The p16 methylation in oral leukoplakia and oral squamous cell carcinoma].

OBJECTIVE: To investigate p16 gene methylation in normal mucosa, leukoplakia with hyperplasia and dysplasia and oral squamous cell carcinoma. METHODS: 20 patients of leukoplakia with hyperplasia, 11 patients of leukoplakia with mild dysplasia, 10 patients of leukoplakia with moderate dysplasia, 9 patients of leukoplakia with severe dysplasia, 10 patients with OSCC in low grade, 12 patients with OSCC in moderate grade, 8 patients with OSCC in high grade, and 10 normal individuals were studied on p16 methylation. RESULTS: Rates of p16 methylation were 0 for normal individuals, 5% for patients of leukoplakia with hyperplasia, 18% for patients of leukoplakia with mild dysplasia, 10% for patients of leukoplakia with moderate dysplasia, 22% for patients of leukoplakia with moderate dysplasia, and 50% for patients with OSCC in low grade, 42% for patients with OSCC in moderate grade, and 63% for patients with OSCC in high grade. Rates of p16 methylation increased with tissue malignance increase and correlated positively to the tissue malignance. The rate (82%) of p16 methylation in OSCC patients with lymph node metastasis was significantly high than that (32%) of OSCC patients without lymph nodes metastasis. The methylated rates of p16 correlated positively to the lacking rates of p16 protein. CONCLUSIONS: It was first reported that p16 methylation occurred in every stage of leukoplakia cancerization and OSCC progression. p16 can be one of the important molecular biological markers for leukoplakia cancerization and OSCC progression. p16 methylation is recommended as an important marker for diagnosis of OSCC.

Adult↗

DNA content as a prognostic marker in patients with oral leukoplakia.

BACKGROUND: Oral leukoplakia may develop into squamous-cell carcinoma, which has a poor prognosis. Risk factors for oral carcinoma have been identified, but there are no reliable predictors of the outcome in individual patients with oral leukoplakia. METHODS: We identified 150 patients with oral leukoplakia that was classified as epithelial dysplasia and measured the nuclear DNA content (ploidy) of the lesions to determine whether DNA ploidy could be used to predict the clinical outcome. Biopsy specimens obtained at annual follow-up visits were graded histologically and classified with respect to DNA content in a blinded fashion. Disease-free survival was assessed in relation to DNA ploidy and the histologic grade. The mean duration of follow-up was 103 months (range, 4 to 165). RESULTS: Among 150 patients with verified epithelial dysplasia, a carcinoma developed in 36 (24 percent). Of the 150 patients, 105 (70 percent) had diploid (normal) lesions, 20 (13 percent) had tetraploid (intermediate) lesions, and 25 (17 percent) had aneuploid (abnormal) lesions at the time of the initial diagnosis. A carcinoma developed in 3 of the 105 patients with diploid lesions (3 percent), as compared with 21 of the 25 patients with aneuploid lesions (84 percent), yielding a negative predictive value of 97 percent with respect to the diploid lesions and a positive predictive value of 84 percent with respect to the aneuploid lesions. Carcinoma developed in 12 of 20 patients with tetraploid lesions (60 percent). The mean time from the initial assessment of the DNA content to the development of a carcinoma was 35 months (range, 4 to 57) in the group with aneuploid lesions and 49 months (range, 8 to 78) in the group with tetraploid lesions (P=0.02). The cumulative disease-free survival rate was 97 percent among the group with diploid lesions, 40 percent among the group with tetraploid lesions, and 16 percent among the group with aneuploid lesions (P<0.001). CONCLUSIONS: The DNA content in cells of oral leukoplakia can be used to predict the risk of oral carcinoma.

Biomarkers, Tumor↗

Loss of expression of DNA repair enzyme MGMT in oral leukoplakia and early oral squamous cell carcinoma. A prognostic tool?

MGMT is a specific DNA repair enzyme that removes alkylating lesions and therefore plays an important role in maintaining normal cell physiology and genomic stability. Loss of expression of MGMT is associated with increased carcinogenic risk and sensitivity to methylating agents in different types of tumours. The expression of MGMT was immunohistochemically assessed in 12 normal oral mucosa, 38 oral leukoplakias and 33 early oral squamous cell carcinomas. The results were correlated with clinicopathological data. We found a significant loss of MGMT protein expression from leukoplakia when compared with early squamous cell carcinoma. We also observed a statistically significant relationship between smoking and the loss of MGMT protein expression. Loss of MGMT expression could be considered an early event in oral carcinogenesis with possible prognostic implications.

Adult↗

Interventions for treating oral leukoplakia.

BACKGROUND: Oral leukoplakia is a relatively common oral lesion that in a small but significant proportion of cases changes into cancer. Since most leukoplakias are asymptomatic, the primary objective of treatment should be to prevent such malignant transformation. OBJECTIVES: To assess effectiveness, safety and acceptability of treatments for leukoplakia. SEARCH STRATEGY: The following databases were searched for relevant trials: Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE. Handsearching was performed for the main oral medicine journals. References of included studies and reviews were checked. Oral medicine experts were contacted through an European mailing list (EURORALMED). SELECTION CRITERIA: Randomised controlled trials (RCTs), enrolling patients with a diagnosis of oral leukoplakia, were included. Any surgical or medical (topical and systemic) treatment was included. The primary outcome considered was malignant transformation of leukoplakia. Other outcomes considered were clinical resolution, histological modification and frequency of adverse effects. DATA COLLECTION AND ANALYSIS: Data were collected using a specific extraction form. Malignant transformation of leukoplakia, demonstrated by histopathological examination, was the main outcome considered. Secondary outcomes included clinical resolution of the lesion and variation in dysplasia severity. The validity of included studies was assessed by two reviewers, on the basis of the method of allocation concealment, blindness of the study and loss of participants. Data were analysed by calculating relative risk. When valid and relevant data were collected, a meta-analysis of the data was undertaken. MAIN RESULTS: The possible effectiveness of surgical interventions, including laser therapy and cryotherapy, has never been studied by means of a RCT. Nineteen potentially eligible RCTs of non-surgical interventions were identified: eight were excluded for different reasons, four were ongoing studies, leaving seven studies to be included in the review. Two studies resulted at low risk of bias, four at moderate risk of bias and one at high risk of bias. Vitamin A and retinoids were tested by five RCTs (245 patients), the other drugs tested were bleomycin (one study), mixed tea (one study) and beta carotene (one study). Malignant transformation was recorded in just two studies: none of the treatments tested showed a benefit when compared with the placebo. Treatment with beta carotene and vitamin A or retinoids, was associated with significant rates of clinical resolution, compared with placebo or absence of treatment. Whenever reported, a high rate of relapse was a common finding. Side effects of variable severity were often described; however, interventions were well accepted by patients, since drop-out rates were similar between treatment and control groups. REVIEWERS' CONCLUSIONS: To date there is no evidence of effective treatment in preventing malignant transformation of leukoplakia. Treatments may be effective in the resolution of lesion, however relapses and adverse effects are common.

Humans↗

Interventions for treating oral leukoplakia.

BACKGROUND: Oral leukoplakia is a relatively common oral lesion that in a small but significant proportion of cases changes into cancer. Since most leukoplakias are asymptomatic, the primary objective of treatment should be to prevent such malignant transformation. OBJECTIVES: To assess effectiveness, safety and acceptability of treatments for leukoplakia. SEARCH STRATEGY: The following databases were searched for relevant trials: Cochrane Oral Health Group's Trials Register (to April 2006), CENTRAL (TheCochrane Library 2006, Issue 1), MEDLINE (from 1966 to December 2005), and EMBASE (from 1980 to December 2005). Handsearching was performed for the main oral medicine journals. References of included studies and reviews were checked. Oral medicine experts were contacted through an European mailing list (EURORALMED). SELECTION CRITERIA: Randomised controlled trials (RCTs), enrolling patients with a diagnosis of oral leukoplakia, were included. Any surgical or medical (topical and systemic) treatment was included. The primary outcome considered was malignant transformation of leukoplakia. Other outcomes considered were clinical resolution, histological modification and frequency of adverse effects. DATA COLLECTION AND ANALYSIS: Data were collected using a specific extraction form. Malignant transformation of leukoplakia, demonstrated by histopathological examination, was the main outcome considered. Secondary outcomes included clinical resolution of the lesion and variation in dysplasia severity. The validity of included studies was assessed by two review authors, on the basis of the method of allocation concealment, blindness of the study and loss of participants. Data were analysed by calculating risk ratio. When valid and relevant data were collected, a meta-analysis of the data was undertaken. MAIN RESULTS: The possible effectiveness of surgical interventions, including laser therapy and cryotherapy, has never been studied by means of a RCT with a no treatment/placebo arm. Twenty-five eligible RCTs of non-surgical interventions were identified: 11 were excluded for different reasons, five were ongoing studies, leaving nine studies to be included in the review (501 patients). Two studies resulted at low risk of bias, six at moderate risk of bias and one at high risk of bias. Vitamin A and retinoids were tested by five RCTs, two studies investigated beta carotene or carotenoids, the other drugs tested were bleomycin (one study), mixed tea (one study) and ketorolac (one study). One study tested two treatments. Malignant transformation was recorded in just two studies: none of the treatments tested showed a benefit when compared with the placebo. Treatment with beta carotene, lycopene and vitamin A or retinoids, was associated with significant rates of clinical resolution, compared with placebo or absence of treatment. Whenever reported, a high rate of relapse was a common finding. Side effects of variable severity were often described; however, interventions were well accepted by patients, since drop-out rates were similar between treatment and control groups. AUTHORS' CONCLUSIONS: To date there is no evidence of effective treatment in preventing malignant transformation of leukoplakia. Treatments may be effective in the resolution of lesion, however relapses and adverse effects are common.

Humans↗

Interventions for treating oral leukoplakia.

BACKGROUND: Oral leukoplakia is a relatively common oral lesion that in a varying proportion of cases undergoes malignant transformation. Since most leukoplakias are asymptomatic, the need for treatment is primarily based on the precancerous nature of the lesion. OBJECTIVES: To assess effectiveness, safety and acceptability of treatments for leukoplakia. SEARCH STRATEGY: The following data bases were searched for relevant trials: MEDLINE, EMBASE, CancerLit, Biological Abstracts, Cochrane library. Hand searching was performed for the main oral medicine journals. Oral medicine experts were contacted through an European mailing list (EURORALMED). SELECTION CRITERIA: Randomised controlled trials (RCTs), enrolling patients with a diagnosis of oral leukoplakia, were included. DATA COLLECTION AND ANALYSIS: Data were collected using a specific abstraction form. Malignant transformation of leukoplakia, demonstrated by histopathological examination, was the main outcome considered. Secondary outcomes included clinical resolution of the lesion and variation in dysplasia severity. The validity of included studies was assessed on the basis of the method of allocation concealment, blindness of the study and loss of participants. Data were analysed by calculating relative risk. MAIN RESULTS: The possible effectiveness of surgical interventions, including laser therapy and cryotherapy, has apparently never been studied by means of a RCT. Fourteen potentially eligible RCTs of nonsurgical intervention were identified: five were excluded for different reasons, three were ongoing studies, leaving six studies to be included in the review. Vitamin A and retinoids were tested by four RCTs (224 patients), the other drugs tested were bleomycin (one study), mixed tea (one study) and beta carotene (one study). Malignant transformation was recorded in just two studies: none of the treatments tested showed a benefit when compared with the placebo. Treatment with beta carotene and vitamin A or retinoids, was associated with better rates of clinical remission, compared with placebo or absence of treatment. Whenever reported, a high rate of relapse was a common finding. Side effects of variable severity were often described; however, interventions were well accepted by patients, since drop-out rates were similar between treatment and control groups. REVIEWER'S CONCLUSIONS: To date there is no evidence of effective treatment in preventing malignant transformation of leukoplakia. Treatments may be effective in the resolution of lesion, however relapses and adverse effects are common.

Humans↗