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Reactivity of monoclonal antibodies 17.13 and 63.12 with oral epithelial dysplasia and hyperkeratosis.

Monoclonal antibodies (MAbs) 17.13 and 63.12 exhibit characteristic reactivity patterns in normal stratified squamous epithelium, as well as highly sensitive and specific altered reactivity patterns in squamous cell carcinoma. The purpose of this study was to critically evaluate the patterns of reactivity of MAbs 17.13 and 63.12 in 43 biopsies of clinical oral leukoplakia or erythroleukoplakia with microscopic diagnoses of hyperkeratosis or epithelial dysplasia. Altered carcinoma-like reactivity patterns were seen in 72% of hyperkeratoses and in all cases of epithelial dysplasia, but varied in the level of epithelial strata exhibiting altered reactivity. Increased frequency of altered reactivity within the epithelial strata was associated with the presence, but not the grade of, epithelial dysplasia, as well as with the presence, intensity; and pattern of submucosal inflammation. The results of this study suggest that altered reactivity patterns of MAb 17.13 are associated with epithelial dysplasia and may be of assistance in detecting precancerous changes in hyperkeratoses before morphologically identifiable epithelial dysplasia. The association of submucosal inflammation with altered MAbs 17.13 and 63.12 reactivity may indicate either a decrease in specificity of these antibodies for precancerous change or an increased significance of inflammation in precancerous lesions.

Antibodies, Monoclonal↗

The pattern of expression of the 5T4 oncofoetal antigen on normal, dysplastic and malignant oral mucosa.

The human 5T4 oncofoetal antigen is expressed by all types of trophoblast in pregnancy but is not detected on most adult tissues, although low levels are found on some epithelia. However, this antigen is strongly expressed by many cancers and tumour-associated labelling correlates with metastatic spread and poor clinical outcome for patients with gastric and colon cancer. Over-expression of the gene influences cell adhesion, shape and motility, which may be related to changes in the cellular localisation of the 5T4 oncofoetal antigen as malignancy develops. To establish whether the 5T4 oncofoetal antigen can serve as a tumour-specific marker for oral cancer and precancer, we have evaluated the pattern of expression on biopsies of normal, inflamed and dysplastic oral mucosa using immunohistochemistry. Oral mucosa, taken from different sites in the mouth, expressed the 5T4 oncofoetal antigen with varying intensity and pattern. The majority of the immunoreactivity was detected in the basal and suprabasal layers, with expression extending into the spinous cells at fully keratinised sites and when inflammation was present. This antigen was also detected in the underlying connective tissue. Oral squamous cell carcinoma showed a variety of patterns and intensity of staining corresponding to those found for normal mucosa. However, 21 of 41 cases showed no stromal labelling, a finding also observed for dysplastic lesions. The alterations in the pattern and intensity of 5T4 oncofoetal antigen expression were not related to clinicopathological features of the tumours examined. These data show that the 5T4 oncofoetal antigen is expressed on normal oral mucosa, such that this target cannot be used for detection of neoplastic or preneoplastic cells, although altered expression may contribute to the pathogenesis of these lesions.

Adult↗

Comparison of BrdU and cyclin A as markers of the S-phase in oral precancerous lesions.

A study comparing bromodeoxyuridine (BrdU) and cyclin A as markers of cells in the S-phase in oral precancerous lesions was performed. These were also compared with the growth fraction (GF) as assessed by Ki-67. Biopsies of 15 lesions were obtained, presenting clinically as leukoplakia or erythroplakia of the lateral tongue or floor of mouth. Half of each biopsy was incubated in BrdU and routinely fixed and processed. Sequential sections from each block were cut and stained immunohistochemically with antibodies against the following proteins: BrdU, Ki-67 and cyclin A. Stained sections were quantified and the labelling indices (LI) expressed per 100 of the total nucleated cell population (%) and per millimetre basement length (/mm). The mean LI% for BrdU was 11.24% (SD 2.83), for cyclin A it was 12.76% (SD 3.88) and the GF% was 29.25% (SD 11.88). The mean LI/mm for BrdU was 40.93/mm (SD 11.88), for cyclin A it was 47.59/mm (SD 18.28) and the GF/mm was 110.72/mm (SD 49.30). The BrdU and cyclin A indices were significantly correlated with each other. In the more dysplastic cases, the cyclin A LI was quantitatively much larger than that for BrdU, suggesting that the protein was being overexpressed. It was concluded that as a tool to study the kinetic aspects of the cell cycle in dysplastic lesions cyclin A was limited by the fact that it is overexpressed. In minimally dysplastic lesions and normal epithelia, however, cyclin A may be a viable alternative to BrdU for the study of the S-phase.

Adult↗

Progress in determining the malignant potential of oral lesions.

The dilemma in managing patients with potentially malignant oral lesions and field change is of deciding which mucosal lesions or areas will progress to carcinoma. Although dysplasia may be predictive, this is not invariable, and there can be considerable inter- and intraexaminer variation in that diagnosis. Recent data on molecular and DNA changes in potentially malignant lesions suggest that it is now feasible to identify those lesions that are truly potentially malignant.

Biomarkers, Tumor↗

Frequent gene deletions in potentially malignant oral lesions.

Some oral cancers are preceded by premalignant lesions which include leucoplakia and erythroplakia. At present there are no reliable markers to identify lesions that may progress to malignancy. We have analysed 30 potentially malignant oral lesions for deletions at chromosomal regions that harbour tumour-suppressor genes for oral cancer. A total of 16 of 30 cases (53%) showed loss of heterozygosity (LOH) or allele imbalance at TP53, DCC, 3p21.3-22.1 or 3p12.1-13. These genetic alterations were detected in dysplastic lesions but not in histologically normal mucosa and may be early events in the carcinogenic process. A total of 64% of dysplastic lesions that recurred during the study showed LOH or allele imbalance in the initial biopsy and the number of genetic abnormalities increased in the tumours that developed. This type of molecular profiling may help to identify patients with lesions that may recur or acquire additional genetic events and progress to malignancy.

Adult↗

Prevention and detection of oral cancer: the views of primary care dentists in Northern Ireland.

Our objective was to describe the management of oral cancer and pre-cancer as stated by primary care dentists and their views on screening. We conducted a survey of all general dental practitioners and community dentists in Northern Ireland (n = 635), to which 428 replied (response rate: 67%). 94% stated that examination of the oral soft tissues constituted part of their usual practice during the regular dental check-up. Suspicious lesions were generally referred early, 68.5% of dentists referring white lesions within one month of presentation. The corresponding figures for red lesions, lumps and persistent ulcers were 80.1%, 89.7% and 91.7%. The incidence of oral cancer was over-estimated (median '70' cases/year, versus the true figure of approximately 40/year) as, in all likelihood, was the percentage by which mortality could be reduced by screening (median: 50%). Accordingly the adoption of a screening programme was favoured over investment in health promotion. Indeed, only 14% said that their patients records routinely contained information about smoking or alcohol habits. Although there are some areas of practice which could improve and the potential of screening is probably over-valued, primary care dentists in Northern Ireland already opportunistically screen and refer patients promptly.

Alcohol Drinking↗

Oral medicine--update for the dental practitioner: red and pigmented lesions.

This series provides an overview of current thinking in the more relevant areas of oral medicine for primary care practitioners, written by the authors while they were holding the Presidencies of the European Association for Oral Medicine and the British Society for Oral Medicine, respectively. A book containing additional material will be published. The series gives the detail necessary to assist the primary dental clinical team caring for patients with oral complaints that may be seen in general dental practice. Space precludes inclusion of illustrations of uncommon or rare disorders, or discussion of disorders affecting the hard tissues. Approaching the subject mainly by the symptomatic approach--as it largely relates to the presenting complaint--was considered to be a more helpful approach for GDPs rather than taking a diagnostic category approach. The clinical aspects of the relevant disorders are discussed, including a brief overview of the aetiology, detail on the clinical features and how the diagnosis is made. Guidance on management and when to refer is also provided, along with relevant websites which offer further detail.

Erythroplasia↗

Interventional laser surgery: an effective surgical and diagnostic tool in oral precancer management.

Invasive oral squamous cell carcinomas (OSCCs) are often preceded by precancerous lesions, the management of which remains controversial, polarized between active surgical excision to try to prevent malignant change or more conservative, medical or observational techniques. In order to determine the efficacy of interventional CO2 laser surgery in oral precancer management, the records of 57 consecutive laser-treated patients presenting over a 4-year period, with histologically confirmed dysplastic lesions, were reviewed. Leukoplakias were the commonest clinical lesions (69%), whilst the floor of the mouth was the most frequent anatomical site (42%). Laser surgery successfully excised 55 precancerous lesions, 11 of which exhibited more severe dysplasia or neoplasia compared with initial biopsy. Postoperative scarring and morbidity were minimal. After surgery, patients were followed for between 1 and 44 months (mean 18 months). Of these patients, 76% remained disease-free, whilst 24% developed new dysplastic lesions at distinct or multiple sites, often exhibiting increased dysplasia. Of the patients experiencing recurrence, 7% developed OSCC, whilst a further 3.5% presented with other aerodigestive tract cancers. Neither initial lesion appearance nor histological diagnosis predicted clinical behaviour. Interventional laser surgery is thus advised, in contradistinction to conservative management of oral precancers, to facilitate efficacious, low-morbidity treatment and to establish definitive histological diagnosis. As a consequence of field change carcinogenesis, regular follow up of treated precancer patients is mandatory for effective tertiary prevention.

Adult↗

Lack of association between hepatitis C virus and oral epithelial dysplasia in British patients.

Oral lichen planus may be a premalignant condition. An association between hepatitis C virus (HCV) infection and oral lichen planus has been described in Southern European and Japanese patients, and recently an association between HCV and oral squamous cell carcinoma was suggested from a study of Japanese patients. The present study investigated the frequency of chronic liver disease and HCV infection in UK patients with oral epithelial dysplasia (OED), a known premalignant disorder. Subjects included 75 patients with histologically proven OED and 110 healthy controls. Liver function and IgG antibodies to HCV were examined serologically. No patient with OED or control subject had serological evidence of hepatic disease, and anti-HCV antibodies were detected in only two (2.6%) of the 75 patients with OED, none of the controls being HCV seropositive. It is concluded that in the UK there is no association between HCV infection and OED.

Adult↗

Intraoral grafting of an ex vivo produced oral mucosa equivalent: a preliminary report.

The objective of this study was to assess the efficacy of the use of an ex vivo produced oral mucosa equivalent (EVPOME) for intraoral grafting procedures. Autogenous keratinocytes were harvested from a punch biopsy 4 weeks prior to surgery, placed in a serum-free culture system and seeded onto a human cadaveric dermal equivalent, AlloDerm. Thirty patients with either a premalignant or cancerous lesion were triaged into two groups, depending on the stage of disease: Group 1: EVPOME or Group 2: AlloDerm, control without an epithelial layer. Clinically, EVPOME grafts were easy to handle and showed excellent compliance on grafting. Both, EVPOME and AlloDerm grafts, showed a 100% take rate. At 6 days post-grafting, the EVPOME clinically showed changes indicating vascular ingrowth and had cytologic evidence of the persistence of grafted cultured keratinocytes on the surface. The EVPOME grafts had enhanced maturation of the underlying submucosal layer associated with rapid epithelial coverage when compared to the AlloDerm grafts at biopsies taken at 28 days post-grafting. In summary, EVPOME appears to be an acceptable oral mucosal substitute for human intraoral grafting procedures and results in a more favorable wound healing response than AlloDerm alone.

Adult↗

[Precancer stages of the oral mucosa: a review].

UNLABELLED: According to the WHO collaborating centre precancerous lesions and precancerous conditions have to be distinguished. Precancer: BACKGROUND: Erythroplakia is the most dangerous precancerous lesion. It is rare, but may often remain undetected. It will transform into cancer within five years and therefore, has to be excised in every case. Leukoplakias show malignant transformation in 3-45% of the cases. In spite of modern molecular biological and immunohistochemical techniques the clinical appearance and the histological grading of the dysplasia are still most important prognostic factors. Until 1992 every lesion showing signs of moderate and severe dysplasia was excised in our department. Despite this treatment strategy 6.2% of the leukoplakias (n = 161) transformed into cancer. Therefore, we recommend to remove every lesion which does not disappear after eliminating the etiological factors. METHODS: Since 1992 168 leukoplakias were completely removed using the CO2 Laser and underwent histological examination. RESULTS: In 3% of these cases a carcinoma was detected in the leukoplakia; 5% of the lesions recurred. Precancerous condition: The most important precancerous condition, the oral lichen planus is treated in cases of erosive lesions only or if the patient is suffering from the symptoms. Malignant transformation is seen in 1.5% of the patients within 10 to 15 years. Histologically the oral lichen planus does not differ from the oral lichenoid reactions, lesions in contact with amalgam restorations mostly. In these cases a causative treatment with replacement of the amalgam is recommended.

Candidiasis, Oral↗

Head and neck cancer.

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Cell Transformation, Neoplastic↗

Oral precancerous and malignant lesions associated with graft-versus-host disease: report of 2 cases.

The development of secondary malignancies has been recognized as a potential iatrogenic complication in patients who have graft-versus-host disease secondary to bone marrow transplantation. Lymphohematopoietic cancer is most frequent, although solid malignancies have also been reported. We describe 2 patients with graft-versus-host disease who developed oral precancerous and malignant lesions. The first patient, a 24-year-old white man, had erythroplakia of the buccal mucosa that proved to be carcinoma in situ histopathologically. The second patient, a 14-year-old Hispanic boy, developed synchronous cutaneous and lingual squamous cell carcinomas. The current cases and similar sporadic case reports found in the literature highlight the susceptibility of patients with graft-versus-host disease to the development of oral cancer. Therefore, it is recommended that thorough evaluation of the oral mucosa and close follow-up be offered to all patients treated with bone marrow transplantation and particularly to those who develop graft-versus-host disease.

Adolescent↗