Alterations in Factors Involved in Differentiation and Barrier Function in the Epithelium in Oral and Genital Lichen Planus.

Lichen planus is a chronic recurrent inflammatory disease affecting both skin and mucosa, mainly in oral and/or genital regions. Keratinocytes go through a well-regulated process of proliferation and differentiation, alterations in which may result in defects in the protective epithelial barrier. Long-term barrier impairment might lead to chronic inflammation. In order to broaden our understanding of the differentiation process in mucosal lichen planus, we mapped the expression of 4 factors known to be involved in differentiation. Biopsies were collected from oral and genital lichen planus lesions and normal controls. Altered expression of all 4 factors in epithelium from lichen planus lesions was found, clearly indicating disturbed epithelial differentiation in lichen planus lesions.

Genes involved in epithelial differentiation and development are differentially expressed in oral and genital lichen planus epithelium compared to normal epithelium.

Lichen planus (LP) is a chronic mucocutaneous disease with unknown cause. Patients with LP often have both oral and genital lesions, but these conditions are often considered as separate diseases and treated accordingly. To find out which genes are differently expressed in mucosal LP compared to normal mucosa and establish whether oral and genital LP are in fact the same disease, whole genome expression analysis was performed on epithelium from 13 patients diagnosed with oral and/or genital LP and normal controls. For confirmation of keratin 4 and corneodesmosin expression, quantitative reverse-transcription PCR and immunohistochemistry were used. Many genes involved in epithelial development and differentiation are differently expressed in epithelium from LP compared to normal epithelium. Several of the differentially expressed genes are common for oral and genital LP and the same biological processes are altered which supports the fact that oral and genital LP are manifestations of the same disease. The change in gene expression indicates that differentiation is altered leading to changes in the epithelial barrier.

Mucosal lichen planus, a systemic disease requiring multidisciplinary care: a cross-sectional clinical review from a multidisciplinary perspective.

OBJECTIVE: This study aimed to emphasize the importance of seeing mucosal lichen planus (LP) as a systemic disease and not an isolated oral or genital disease and to analyze the proportion of thyroid antibodies among patients with multimucosal LP. MATERIALS AND METHODS: All patients examined by the authors and diagnosed with mucosal LP within 1 year were consecutively included. Full medical histories were collected with special emphasis on autoimmune and thyroid diseases. Sera were analyzed for thyroid antibodies and underwent serologic test for herpes virus. The control group comprised 83 healthy volunteers matched regarding sex and age. RESULTS: Of the patients, 120 were included, 89 (74%) of whom were women and 31 (26%) were men. The vast majority of the patients had multifocal lesions, whereas oral lesions solely were found in 28% of women and 36% of men. Of the patients, 28% had at least 1 additional autoimmune disease. Approximately half of the women were treated with levothyroxine owing to thyroid disease. Antibodies against herpes simplex virus were found in 60% of the patients and 44% of the controls (p < .03). CONCLUSIONS: Lichen planus with mucosal involvement should be considered and taken care of as a systemic disease and not as an isolated oral and/or genital lichen. Contradictory to many former reports, most of our patients have a multimucosal disease that emphasizes the need for a multidisciplinary clinic to get optimal care and treatment.

Changes in miRNA expression in sera and correlation to duration of disease in patients with multifocal mucosal lichen planus.

BACKGROUND: Mucosal lichen planus is a severe variant of lichen planus, Lichen planus (LP), which in many ways affect patients' lives. The aetiology is not fully understood, and there is no treatment clearing the disease once and for all. Oral LP has by the WHO been classified as a precancerous lesion. Micro-RNAs, miRNAs, are non-coding, small single-stranded RNAs involved in biological processes like apoptosis, proliferation, differentiation, metastasis, angiogenesis and immune response. METHODS AND RESULTS: In sera from 30 patients with multifocal mucosal LP, 15 miRNAs were identified as significantly differentially expressed compared with controls. The three most up-regulated miRNAs are all connected to oral squamous cell carcinoma or epithelial carcinoma in general. DISCUSSION: Even if no specific LP-associated miRNA profile was found, data clearly indicate that miRNAs could play a role in the earlier phases of lichen planus.

The use of a novel ELISA method for detection of antibodies against p63 in sera from patients diagnosed with oral and/or genital and skin lichen planus.

Lichen planus is a chronic inflammatory disease of mucosa and skin affecting approximately 1-2% of the adult population. Autoimmunity has been implicated in the etiology of this disease, and recently we detected antibodies directed against all six p63 isoforms in sera from 2 out of 20 patients diagnosed with oral lichen planus (OLP) using Western blot analysis. Here we have developed an ELISA method for screening sera for presence of autoantibodies directed against p63. Using the same sera as previously analysed, we show that the optical density ratios for sera from the two patients with known autoantibodies was considerably higher compared to mean optical density ratios for all samples as well as controls analysed. Applying this novel ELISA technique for screening of sera from an additional group of 46 patients with oral and/or genital or skin lichen and 43 matched controls, we detected another three patients with autoantibodies against the p63 proteins. These data are discussed together with the observation that all five patients with detectable p63 autoantibodies from our two studies had clinically severe disease symptoms.

Decreased expression of the p63 related proteins beta-catenin, E-cadherin and EGFR in oral lichen planus.

Oral lichen planus (OLP) is a chronic inflammatory disease and although classified by WHO as a premalignant condition, the risk for transformation into squamous cell carcinoma of the head and neck (SCCHN) is a matter of great controversy. The p63 gene encodes six different proteins which are required for development of ectodermally derived tissues such as oral mucosa, salivary glands, teeth and skin. p63 is highly expressed in SCCHN whereas decreased expression is seen in OLP. beta-catenin, E-cadherin and epidermal growth factor receptor (EGFR) are p63 related proteins, and abnormalities in their expression suggested they are involved in development of squamous cell carcinoma of the head and neck (SCCHN). In this study we mapped the expression of these p63 related proteins in OLP and matched normal healthy controls. Results showed decreased expression of beta-catenin, E-cadherin and EGFR in the vast majority of OLP samples compared with the normal controls. This is the first comprehensive study mapping expression of several p63- and SCCHN-related proteins in tissue from patients with OLP. Results showed a mixed expression pattern with OLP variably resembling normal as well as tumour tissue. Based on our present and previous data it cannot be judged whether OLP lesions are at an increased risk of malignant development.

Expression of novel p53 isoforms in oral lichen planus.

Oral lichen planus (OLP) is a chronic inflammatory disease of unknown origin, showing little spontaneous regression. WHO classifies OLP as a premalignant condition, however, the underlying mechanisms initiating development of cancer in OLP lesions are not understood. The p53 tumour suppressor plays an important role in many tumours, and an increased expression of p53 protein has been seen in OLP lesions. Recently it was shown that the human TP53 gene encodes at least nine different isoforms. Another member of the p53 family, p63, comprises six different isoforms and plays a crucial role in the formation of oral mucosa, salivary glands, teeth and skin. It has also been suggested that p63 is involved in development of squamous cell carcinoma of the head and neck (SCCHN). In contrast to p53, a decreased expression of p63 protein has been seen in OLP lesions. In this study, we mapped the expression of five novel p53 isoforms at RNA and protein levels in OLP and matched normal controls. In the same samples we also measured levels of p63 isoforms using quantitative RT-PCR. Results showed p53 to be expressed in all OLP lesions and normal tissues. The p53 beta and delta 133p53 isoforms were expressed in the majority of samples whereas the remaining three novel isoforms analysed were expressed in only a few samples. Levels of p63 isoforms were lower in OLP lesions compared with normal tissue, however, changes were not statistically significant.

Detection of antibodies against p63 and p73 isoforms in sera from patients diagnosed with oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease of oral mucosa. Despite numerous publications and intense research, the etiology of OLP is still unknown, however, autoimmunity as a possible causative factor has been discussed. METHODS: In the present study sera from 20 patients clinically and histologically diagnosed with OLP were analyzed for antibodies directed toward p53, p63, and p73 using Western blot. RESULTS: Sera from two patients reacted with all six p63 isoforms, and one also with p73. The strongest reaction was noted against the TAp63beta protein, which is the most potent transactivator of all p63 proteins and is implicated in the differentiation of stratified epithelia. CONCLUSIONS: This is the first demonstration of antibodies directed against all p63 and some p73 isoforms in sera from patients diagnosed with OLP.

Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia.

BACKGROUND: Patients with Kostmann syndrome (severe congenital neutropenia [SCN]) typically normalize their absolute neutrophil count (ANC) upon granulocyte colony-stimulating factor (G-CSF) therapy. However, although they no longer experience life-threatening bacterial infections, they frequently still have recurrent gingivitis and even severe periodontitis, often starting in early childhood. METHODS: We studied the periodontal disease in the four surviving patients belonging to the family originally described by Kostmann. Their odontological records, x-rays, color photos, bacterial cultures, serum antibodies to oral bacteria, and histopathological examinations were reviewed. The data were also correlated to previous investigations on their antibacterial peptides and molecular biology. RESULTS: Three patients had periodontal disease, despite normal ANC and professional dental care, and had neutrophils deficient in antibacterial peptides. One of these patients also had a heterozygous mutation in the neutrophil elastase gene, had severe periodontal disease and overgrowth of the periodontal pathogen Actinobacillus actinomycetemcomitans in the dental flora, and 15 permanent teeth had been extracted by the age of 27. One bone marrow-transplanted patient had no periodontal disease. CONCLUSIONS: Normalized ANC levels are not sufficient to maintain normal oral health in SCN patients, and because neutrophils are important for first-line defense and innate immunity, the deficiency of the antibacterial peptide LL-37 probably explains their chronic periodontal disease. Professional dental care is still important for SCN patients, despite treatment with G-CSF and normal ANC levels. Whether antibacterial peptides play a role in the pathogenesis of periodontitis in other patients remains to be elucidated.

Altered food intake and taste perception in children with cancer after start of chemotherapy: perspectives of children, parents and nurses.

GOALS OF WORK: The purpose of this study was to better understand various variables related to food intake and eating problems in children with cancer during their chemotherapy. PATIENTS AND METHODS: Twenty-two consecutively admitted children, diagnosed with cancer and undergoing chemotherapy, participated in this study. Twenty-one of them, their parents and attending nurses participated in semi-structured interviews. Ten of the children underwent a taste acuity test, and recognition thresholds for the four basic tastes were determined. MAIN RESULTS: The shared view of both children and parents was that altered taste was the predominant cause of the eating problems. In contrast, the nurses perceived that nausea was the most important cause of the children's eating problems. In addition, psychological aspects such as learned food aversions and negative attitudes towards hospital food were regarded as important by children, parents and nurses. The taste test showed that the patients had higher thresholds for bitter taste and made more taste recognition errors compared to controls. CONCLUSIONS: Changes seem to exist both in the primary gustatory sense as well as in food perception in paediatric cancer patients undergoing chemotherapy. Single solutions, such as efforts to serve "tasty food", do not suffice alone. A more effective solution may be to combine different strategies and combinations of oral, enteral and parenteral nutrition should be considered to prevent malnutrition.

Decreased expression of p63 in oral lichen planus and graft-vs.-host disease associated with oral inflammation.

BACKGROUND: Oral lichen planus (OLP) and graft-vs.-host disease (GVHD) are conditions with increased risk of malignant transformation to squamous cell carcinoma of the head and neck (SCCHN). The p63 gene encodes six different proteins and is expressed at high levels in SCCHN. METHODS: Biopsies from patients diagnosed with OLP and GVHD were analysed for p63 protein expression using antibodies distinguishing between the major isoforms expressed in normal epithelia, in parallel with biopsies from normal buccal mucosa and SCCHN. RESULTS: In OLP and GVHD a decreased expression of all p63 isoforms was seen, while expression of p53 protein was upregulated, compared with normal mucosa. In SCCHN, p63 was abundantly expressed and some tumours showed strong p53 staining, suggestive of p53 mutation. CONCLUSIONS: Decreased p63 and increased p53 expression in OLP and GVHD indicates a coordinated action of these two related proteins to protect the oral mucosae from the damaging effects of underlying inflammation. In SCCHN disruption of the TP53 gene and overrepresentation of certain p63 isoforms has been seen, indicating that this could lead to neoplastic transformation.

Percutaneous endoscopic gastrostomy in children with malignant disease.

The objective of the study was to assess both the possible complications of percutaneous endoscopic gastrostomy (PEG) in pediatric cancer patients and its effect on weight development. The medical records of 18 children with a median age of 2.5 years (range, 0.5-14.2 years) were reviewed. The diagnoses were leukemia, central nervous system tumors, solid tumors, and lymphoma. The indications for PEG were anticipated therapy-related nutritional problems and inadequate food intake, weight loss, swallowing problems in relation to paresis of the pharynx, and relapse of the disease. Ten children received a PEG at treatment start, and eight children received it at a median time of 3.4 months (range, 0.9-27.4 months) after treatment start. The median duration of having a PEG in place was 12.3 months (range, 1.2-24.0 months). At admission the median weight for age expressed as standard deviation (SD) was -0.11 (range, -2.78-2.68). There was a significant (p =.005) decrease in the median SD from admission until PEG installation. There was also a significant increase in the median SD from the start of PEG use until 1 (p =.04) and 2 (p =.039) months after start. The most common complications were episodes of inflammation of the PEG site, which were successfully treated with topically or orally administered antibiotics, and episodes of infection, which required intravenously administered antibiotics. Taking into consideration the medical condition of the children in the study group and the considerable length of time with a PEG in place, we believe that nutrition via PEG in children with cancer has several advantages and is rarely associated with other than minor complications.