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Objectives: The association between obesity and gastroesophageal reflux disease (GERD) is well-established in adults; however, data in pediatric population is scarce. Our study aimed to assess the association between GERD and health-related quality of life (HRQoL) in overweight children., Methods: From April to August of 2020, we included children aged 7-18 years who attended the Endocrinological Outpatient Clinic at the Paediatric Institute, University of Debrecen, Hungary. The participants completed two questionnaires: the Pediatric Gastroesophageal Reflux Disease Symptom Questionnaire (PGSQ) and the HRQoL questionnaire (PedsQL). Based on the criteria of the World Health Organization (WHO), the patients were categorized into two groups: an overweight or obese group and a group with normal weight., Results: A total of 107 children (51 % female, mean age 13.2 years, 46 % overweight or obese) completed the questionnaires. The median PGSQ score was similar in both groups (4.0 (IQR: 1.0-7.8) vs. 3.0 (IQR: 1.0-7.0), p=0.6). However, the total PedsQL score was significantly lower in the children with overweight or obesity compared to those with normal weight (80.1 (71.1-91.0) vs. 88.0 (76.1-94.6), p=0.031). The PedsQL score was lower among overweight patients with GERD symptoms than that of normal-weight patients without GERD symptoms., Conclusions: Our findings highlight the importance of raising awareness about GERD to enhance the HRQoL and prevent long-term complications in obese children., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Innate immune signaling in adipocytes affects systemic metabolism. Cytosolic nucleic acid sensing has been recently shown to stimulate thermogenic adipocyte differentiation and protect from obesity; however, DNA efflux from adipocyte mitochondria is a potential proinflammatory signal that causes adipose tissue dysfunction and insulin resistance. Cytosolic DNA activates the stimulator of interferon response genes (STING), a key signal transducer which triggers type I interferon (IFN-I) expression; hence, STING activation is expected to induce IFN-I response and adipocyte dysfunction. However, we show herein that mouse adipocytes had a diminished IFN-I response to STING stimulation by 2'3'-cyclic-GMP-AMP (cGAMP). We also show that cGAMP triggered autophagy in murine and human adipocytes. In turn, STING inhibition reduced autophagosome number, compromised the mitochondrial network and caused inflammation and fat accumulation in adipocytes. STING hence stimulates a process that removes damaged mitochondria, thereby protecting adipocytes from an excessive IFN-I response to mitochondrial DNA efflux. In summary, STING appears to limit inflammation in adipocytes by promoting mitophagy under non-obesogenic conditions.

MODY2 is caused by heterozygous inactivating mutations in the glucokinase ( GCK ) gene that result in persistent, stable and mild fasting hyperglycaemia (5.6-8.0 mmol/L, glycosylated haemoglobin range of 5.6-7.3%). Patients with GCK mutations usually do not require any drug treatment, except during pregnancy. The GCK gene is considered to be responsible for about 20% of all MODY cases, transcription factors for 67% and other genes for 13% of the cases. Based on our findings, GCK and HNF1A mutations together are responsible for about 90% of the cases in Hungary, this ratio being higher than the 70% reported in the literature. More than 70% of these patients have a mutation in the GCK gene, this means that GCK -MODY is the most prevalent form of MODY in Hungary. In the 91 index patients and their 72 family members examined, we have identified a total of 65 different pathogenic (18) and likely pathogenic (47) GCK mutations of which 28 were novel. In two families, de novo GCK mutations were detected. About 30% of the GCK -MODY patients examined were receiving unnecessary OAD or insulin therapy at the time of requesting their genetic testing, therefore the importance of having a molecular genetic diagnosis can lead to a major improvement in their quality of life.

Maturity-onset diabetes of the young (MODY) has about a dozen known causal genes to date, the most common ones being HNF1A, HNF4A, HNF1B and GCK . The phenotype of this clinically and genetically heterogeneous form of diabetes depends on the gene in which the patient has the mutation. We have tested 450 Hungarian index patients with suspected MODY diagnosis with Sanger sequencing and next-generation sequencing and found a roughly 30% positivity rate. More than 70% of disease-causing mutations were found in the GCK gene, about 20% in the HNF1A gene and less than 10% in other MODY-causing genes. We found 8 pathogenic and 9 likely pathogenic mutations in the HNF1A gene in a total of 48 patients and family members. In the case of HNF1A -MODY, the recommended first-line treatment is low dose sulfonylurea but according to our data, the majority of our patients had been on unnecessary insulin therapy at the time of requesting their genetic testing. Our data highlights the importance of genetic testing in the diagnosis of MODY and the establishment of the MODY subtype in order to choose the most appropriate treatment.

Background: Wolcott-Rallison Syndrome (WRS) is a rare autosomal recessive disease that is the most common cause of neonatal diabetes in consanguineous families. WRS is caused by various genetic alterations of the Eukaryotic Translation Initiation Factor 2-Alpha Kinase 3 (EIF2AK3) gene., Methods: Genetic analysis of a consanguineous family where two children were diagnosed with WRS was performed by Sanger sequencing. The altered protein was investigated by in vitro cloning, expression and immunohistochemistry., Results: The first cases in Hungary, - two patients in one family, where the parents were fourth-degree cousins - showed the typical clinical features of WRS: early onset diabetes mellitus with hyperglycemia, growth retardation, infection-induced multiple organ failure. The genetic background of the disease was a novel alteration in the EIF2AK3 gene involving the splice site of exon 11- intron 11-12 boundary: g.53051_53062delinsTG. According to cDNA sequencing this created a new splice site and resulted in a frameshift and the development of an early termination codon at amino acid position 633 (p.Pro627AspfsTer7). Based on in vitro cloning and expression studies, the truncated protein was functionally inactive. Immunohistochemistry revealed that the intact protein was absent in the islets of pancreas, furthermore insulin expressing cells were also dramatically diminished. Elevated GRP78 and reduced CHOP protein expression were observed in the liver., Conclusions: The novel genetic alteration causing the absence of the EIF2AK3 protein resulted in insufficient handling of severe endoplasmic reticulum stress, leading to liver failure and demise of the patients.

Lethal donkey attacks have very rarely been described. The case of a 65-year-old man who was found deceased on a country road with 2 domestic donkeys nearby is, therefore, reported. Examination of the body revealed contusions and lacerations of the face and scalp, a comminuted fracture of the left maxilla, comminuted fracturing of the right radius and ulna and of the left anterior superior iliac spine, a flail chest, and pulmonary contusions. In addition, there were bite marks on the left thigh, right buttock, right axilla/upper arm, and left cheek which corresponded to the dental arcades of the donkeys. Death had resulted from blunt chest trauma due to an attack by 1 or 2 donkeys. Deaths and serious injuries are much more commonly caused by horses; however, this case shows that even domesticated donkeys may also rarely be capable of inflicting significant trauma and so should be approached with circumspection.

Background Diabetes has previously been linked to mental health problems in children and adolescents, but more recent studies have yielded mixed findings. The aim of the current study was to compare symptoms of mental health problems in children and adolescents with and without type 1 diabetes (T1DM). Methods Life quality, subjective well-being, self-rated health, depression and somatic symptoms in children and adolescents with diabetes (n=130) were measured and compared to the results of a socio-demographically joined control group (n=177) which consists of healthy children and adolescents. Results A significant difference could be observed between the groups in well-being and depressive symptoms as according to the results, the research sample namely the children with T1DM could be described with significantly higher subjective well-being and mood, but with less physical symptoms and lower level of depression as those in the control group. Conclusions These findings suggest that T1DM is not associated with an increased risk of psychosocial problems, and confirm that even a severe disease of a child can lead to personal growth.

Introduction: The isolated haploinsufficiency of the SHOX gene is one of the most common cause of short stature determined by monogenic mutations. The heterozygous deviation of the gene can be detected in 2-15% of patients with idiopathic short stature (ISS), in 50-90% of patients with Leri-Weill dyschondrosteosis syndrome (LWS), and in almost 100% of patients with Turner syndrome., Aim: The aim of our study was to evaluate the frequency of SHOX gene haploinsufficiency in children with ISS, LWS and in patients having Turner syndrome phenotype (TF), but normal karyotype, and to identify the dysmorphic signs characteristic for SHOX gene deficiency., Method: A total of 144 patients were included in the study. Multiplex Ligation-dependent Probe Amplification (MLPA) method was used to identify the SHOX gene haploinsufficiency. The relationships between clinical data (axiological parameters, skeletal disorders, dysmorphic signs) and genotype were analyzed by statistical methods., Results: 11 (7.6%) of the 144 patients showed SHOX gene deficiency with female dominance (8/11, 81% female). The SHOX positive patients had a significantly higher BMI (in 5/11 vs. 20/133 cases, p<0.02) and presented more frequent dysmorphic signs (9/11vs 62/133, p = 0.02). Madelung deformity of the upper limbs was also significantly more frequent among the SHOX positive patients (4/11, i.e. 36%, vs. 14/133, i.e. 10%, p = 0.0066). There were no statistically significant differences between the mean age, mean height and auxological measurements (sitting height/height, arm span/height) between the two groups of patients., Conclusions: The occurrence of SHOX gene haploinsufficiency observed in our population corresponds to the literature data. In SHOX positive patients, in addition to short stature, the dysmorphic signs have a positive predictive value for SHOX gene alterations. However, the SHOX deletion detected in a patient with idiopathic short stature without dysmorphic signs suggest that SHOX deletion analysis can be recommended in patients with ISS. Orv Hetil. 2017; 158(34): 1351-1356.

Purpose: The aim of this study was to quantify epithelial, stromal, and endothelial cell density, and subbasal nerve morphology in young patients with type 1 diabetes mellitus with and without diabetic retinopathy., Methods: A total of 28 young patients (mean age, 22.86 ± 9.05 years) with type 1 diabetes, with (n = 18) and without (n = 10) retinopathy, and 17 age-matched healthy control subjects (mean age, 26.53 ± 2.43 years) underwent corneal confocal microscopy (CCM)., Results: We found significantly lower epithelial (P < 0.0001) and endothelial (P = 0.001) cell densities and higher keratocyte cell density (P = 0.024) in patients with type 1 diabetes compared to controls. Significantly lower corneal nerve fiber density (P = 0.004), nerve branch density (P = 0.004), total nerve branch density (P = 0.04), and nerve fiber length (P = 0.001), and greater nerve fiber width (P = 0.04) were observed in patients with type 1 diabetes compared to control subjects. Significantly lower epithelial (P < 0.001) and endothelial (P = 0.02) cell densities, nerve branch density (P = 0.02), and nerve fiber length (P = 0.04), and significantly higher keratocyte cell density (P = 0.02) were found in patients with type 1 diabetes without retinopathy compared to control subjects., Conclusions: Corneal confocal microscopy identifies corneal cellular and small nerve fiber pathology in young patients with type 1 diabetes without retinopathy, which increases in severity in those with retinopathy. Corneal confocal microscopy appears to have considerable use as an imaging biomarker for early subclinical pathology in young patients with type 1 diabetes mellitus.

Context: Congenital hypothyroidism (CH) is one of the most common inborn endocrine disorders with genetic background. Despite the well-established newborn CH screening program in Hungary, no systematic examination of the underlying genetic alterations has been performed as yet., Objective: We aimed to explore TSH receptor (TSHR) mutations in a cohort of Hungarian patients with CH., Patients: Eighty-five unrelated patients with permanent primary CH, all diagnosed at newborn screening, were selected., Main Outcome Measures: Coding exons of the TSHR gene were sequenced and evaluated together with the thyroid-specific clinical parameters. Functional features of the novel mutations were experimentally examined, and their comparative molecular models were built., Results: In four patients (one heterozygous and three compound heterozygous), seven TSHR mutations were identified. Among these, N432(1.50)D and P449(2.39)L are novel missense alterations. Importantly, the N432(1.50) residue is highly conserved among G protein-coupled receptors, and its function has not been examined yet in human glycoprotein hormone receptors. Our results indicate that the N432(1.50)D mutation disrupts important, architecture-stabilizing intramolecular interactions and ultimately leads to the complete intracellular retention of the receptor. On the other hand, P449(2.39) is located in the intracellular part of the receptor, which is important in G protein coupling. The P449(2.39)L mutation results in signaling impairment, with a more profound effect on the Gq/11 pathway., Conclusion: TSHR mutations are common among Hungarian patients with CH. The novel genetic alterations revealed an important structural role of the N432(1.50) and the P449(2.39) residues in receptor expression and signaling, respectively.

Introduction: Although long-term outcome studies in large pediatric myocarditis/cardiomyopathy populations have been reported in literature, none of them focused on comorbidities., Methods: All children and adolescents (age <18 years) treated with myocarditis at the Department of Pediatrics, University of Debrecen, Hungary were followed. Patients suffering from myocarditis during the period 1996-2011 were enrolled., Results: Over the 16-year period, a diagnosis of myocarditis was established in nine children. Their median age was 1.11 (0.03-8.71) years. Three of the nine patients died. Left ventricular dilatation and ejection fraction normalized within 1-21 months in the survivors. None of the cases progressed to dilated cardiomyopathy. Regarding non-cardiac comorbidities, myocarditis or recurrent peri-myocarditis preceded the manifestation of celiac disease in two patients, while cystic fibrosis was diagnosed after the improvement of cardiac function in another, and Alström syndrome was diagnosed several years after complete recovery from myocarditis in yet another patient., Conclusion: These results suggest that manifestations of other chronic pediatric diseases may be more frequent among survivors of pediatric myocarditis. Prolonged follow-up of patients who survive myocarditis is therefore recommended not only to detect possible progression to cardiomyopathy but also to identify non-cardiac comorbidities.

The association of short stature, microcephaly, congenital cardiac anomaly and intellectual deficit should always raise the suspicion of chromosomal etiology. If G-banded karyotyping fails to detect large chromosomal aberrations, array comparative genomic hybridization (array CGH) should be performed to screen for submicroscopic pathological copy number changes. The authors present a six-year-old girl whose symptoms arose from a 4.1 Mb loss in the 15q26.2-26.3 telomeric region. The syndrome is characterized by a resistance to the insulin-like growth factor 1 - in our case the increased level of the insulin-like growth factor 1 together with the persistent longitudinal growth failure was an important finding and differential diagnostic feature. A brief overview of the literature is provided.

Due to donor side morbidity and the absence of osteogenic properties in bone substitutes, there is a growing need for an alternative to traditional bone grafting within the scope of tissue engineering. This animal study was conducted to compare the in vivo osteogenic potential of adipose-derived (AD), periosteum-derived (PD) and bone marrow-derived (BM) mesenchymal stem/progenitor cells (MSC). Autologous mesenchymal stem/progenitor cells of named tissue origin were induced into osteogenic differentiation following in vitro cell expansion. Ex vivo cultivated cells were seeded on a collagen scaffold and subsequently added to freshly created monocortical calvarial bone defects in 21 domestic pigs. Pure collagen scaffold served as a control defect. The animals were sacrificed at specific time points and de novo bone formation was quantitatively analyzed by histomorphometry. Bone volume/total defect volume (BV/TV) and the mineralization rate of newly formed bone were compared among the groups. In the early stages of wound healing, up to 30 days, the test defects did not show better bone regeneration than those in the control defect, but the bone healing process in the test defects was accelerated in the later stage compared to those in the control defect. All the test defects showed complete osseous healing after 90 days compared to those in the control defect. During the observation period, no significant differences in BV/TV and mineralization of newly formed bone among the test defects were observed. Irrespective of the tissue sources of MSC, the speed and pattern of osseous healing after cell transplantations into monocortical bone defects were comparable. Our results indicate that the efficiency of autologous AD-MSC, PD-MSC and BM-MSC transplantation following ex vivo cell expansion is not significantly different for the guided regeneration of bone defects., (Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Solitary Median Maxillary Central Incisor Syndrome (SMMCI) is a rare malformation syndrome consisting of multiple, mainly midline defects. Some authors suggest that it is a mild manifestation of the wide spectrum of holoprosencephaly, others classify it rather as a distinct entity. Authors report a case of SMMCI presenting with growth retardation, mild intellectual disability and absence of puberty. Cytogenetic and molecular cytogenetic investigations could identify no abnormalities. The presence of a single maxillary incisor called for further investigations to clarify hidden anomalies, these were empty sella, panhypopituitarism, hypothyroidism, and hypoplasia of the inner genitals. Based on the above findings, growth hormone, estrogen, and L-thyroxine substitution was introduced, which resulted in satisfactory longitudinal growth and onset of sexual maturation. We suggest genetic counselling and if needed, invasive investigations in female patients with short stature and absent/delayed puberty, with or without sex chromosomal anomalies, as the adequate therapy and even the quality of life of patient depends largely on the knowledge of their anatomical and endocrine status., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Reconstruction of bone defects with autogenous, autoclaved bone grafts has already been described but does have one major insuperable problem-the loss of the ostoinductive potential of the graft. In this study, we investigated if autogenous, autoclaved grafts in combination with tissue engineered bone can overcome this problem. An en-bloc resection was done in the mandible of eight pigs. The grafts were autoclaved and filled with autogenous, osseogen differentiated bone marrow cells and compared with four animals without bone marrow cells. After 120 days, the specimens were qualitatively and quantitatively evaluated by means of microradiography and light microscopy. Within the experimental group, osseous remodeling was detected in all cases and new bone formation was visible. Quantitative assessment of the osseous bridging of the osteotomy sites was significantly higher in the test group in comparison with the control group (p = 0.03). The histological evaluation by means of an osseous integration of the grafts revealed a statistically significant difference between both groups as well (p = 0.01). The results of this study indicate that the method investigated hereby represents a further possibility in the therapy of bony defects, such as those arising as a result of tumor operations., ((c) 2009 Wiley Periodicals, Inc.)

Introduction: Endosseus implants can provide a reliable anchorage during orthodontic treatment. The midpalatal structures around the sutura palatina mediana (SPM) are of special interest due to increasing placement of orthodontic implants in this area. Knowledge about the osseous conditions at this site is necessary to predict the expected degree of implant osseointegration., Methods: The upper jaws of 10 human cadavers, aged 15-20 years, were decalcified, and cross-sectional specimens were obtained from four anterior-to-posterior palatal regions for histomorphometric analysis. The analyses focused on the amount of bone and the width of the SPM to determine the anatomical requirements for reliable insertion of palatal implants., Results: Bone density [bone-volume (BV)/ tissue-volume (TV)] in all measured areas was 40-60%. The maximum density was measured at the level of the first premolars (54.9+/-5.9%) and the least values (44.2+/-9.6%) were measured at the level of the interconnecting line of the canines. The mean width of the SPM varies from 1.2 to 0.3 mm in different sections of the palate. In the median sagittal plane, the mean values of bone height to nasal cavity reached >5 mm as far as the level distal of the second premolars. Bone height 2 mm paramedian to the SPM decreased consistently from anterior (4.3+/-0.9 mm) to posterior (2.5+/-0.8 mm)., Conclusions: Our results indicate that the amount and quality of bone along the anterior palatal midline in 15-to-20-year olds is sufficient for orthodontic implantation. Even implantation posterior to the recommended first premolar level, at which orthodontic implants are most often placed, may be suitable. There are some limitations, however, due to small number of samples and variations of anatomical structures.

Objectives: The aims of this study were to evaluate the rate of bone formation and osseointegration after topical gene delivery with a liposomal vector system carrying bone morphogenetic protein (BMP)-2 cDNA in combination with a collagen carrier and autologous bone as a carrier in freshly created peri-implant bone defects., Materials and Methods: Eight domestic pigs received nine calvariae defects each (10 x 7 mm). A dental implant was inserted into the centre of each defect. In the test groups, the remaining space was filled with the liposomal vector/BMP-2 complex combined with a collagen carrier (n=18) or an autologous bone graft (n=18). Control groups were collagen only (n=18) and autologous bone graft only (n=18)., Results: There was a significant difference in mineralisation rate in the BMP-2/bone graft (29.9%+/- 4.8 and 68.3%+/- 7.2) and bone graft only (22.6%+/- 2.6 and 49.4%+/- 13.9) groups after 7 and 28 days. Mineralisation values were also significantly higher in the BMP-2/collagen group (21.2%+/- 16.2 and 53.1%+/- 12.5) compared with the collagen-only group (8.2%+/- 7 and 41%+/- 8.1) in two different regions after 28 days. Also the bone-to-implant contact was significantly increased in the BMP-2/bone graft group after 28 days and in the BMP-2/collagen group after 7 and 28 days compared with their control groups., Conclusions: The results of this study show a significantly positive effect of liposomal vector/BMP-2 on bone regeneration and osseointegration in bony circumferential peri-implant defects.

Objective: Different bone substitute materials are used to manage the challenge of local bone loss subsequent to craniofacial reconstructive surgery. In this animal study we examined the de novo bone formation in bone defects after insertion of Puros Allograft of human origin or Navigraft of bovine origin, and compared the regenerative potential of each material to that of autogenous bone., Study Design: Using the adult domestic pig as the animal model, we created identical bone defects in the frontal skull and filled them with the different test materials using random assignment. A defined number of defects remained unfilled to serve as control. We performed microradiographic, histologic, and polychromatic fluorescence labeling evaluations of the bone specimens at 1, 8, and 12 weeks after the procedure., Results: Both of the materials that we tested allowed for complete bony consolidation of the defects by the end of the test period. After 12 weeks, the microradiographically measured mineralization rate was 5% to 10% lower than the mineralization rate of autogenous bone grafts., Conclusion: Both Puros Allograft and Navigraft met the clinical requirements for bone substitutes, promoting predictable regeneration of the bony defects.

Objective: Sinus augmentation is a common approach for patients with severe alveolar ridge atrophy. However, autogenous bone sometimes results in donor site complications. Bone substitutes with platelet-rich plasma (PRP) promote early bone formation with autogenous bone. Use of PRP on autogenous bone and a bovine bone substitute were investigated in this split-mouth animal study., Study Design: Premolars were extracted from minipigs. Each animal received sinus augmentation using a lateral approach with simultaneous insertion of 3 implants in each site. Groups were randomized using autogenous bone alone and combined with PRP or a bovine hydroxyapatite alone in combination with PRP., Results: Microradiographic findings in the autogenous group did not show significantly different rates by using autogenous bone alone or combined with PRP. Using the bovine hydroxyapatite as augmentation material only at 8 weeks, a nonsignificant effect in the PRP group could be seen. At all other observation periods, no significant influence was observed., Conclusion: No significant influence of PRP was found.

Background: Autologous bone is the standard material used for augmentations in oral-maxillofacial surgery. Depending on the origin of the graft, subsequent bone resorption may vary., Study Design: This prospective study evaluated 57 patients receiving 2-stage sinus floor augmentations. Monocortical samples were taken at the site of bone harvesting, including the posterior (n = 28) and anterior pelvic (n = 15) and retromolar (n = 14) regions. At second-stage surgery, 6 months after the implant insertion, bone cores were harvested at the site of implant placement. All samples were analyzed by microradiography., Results: Mean retromolar mineralization was 68.7% +/- 8.75%; 35.1% +/- 7.6% in the anterior and 30.7% +/- 9.5% in the posterior iliac crest. Areas augmented with grafts originating from the retromolar region showed a significant decrease to 53.0% +/- 5.15% (P = .001). A stable mineralization of 36.1% +/- 7.59% was found in sites where bone grafts from the anterior pelvic crest were used. Grafts from the posterior pelvis showed a slight increase to 34.5% +/- 6.5%., Conclusion: This prospective clinical study demonstrates the differences in mineralization depending on the origin of autogenous bone. Even after 6 months, these values could still be correlated to the transplants origin.

The aim of this study was to define whether or not the impaired expression of CD44, E-cadherin (E-cad), and beta-catenin (beta-cat) correlates with the clinical evolution and prognosis of oral cancer. Ninety-three primary oral squamous cell carcinomas (OSCCs) with tumour-adjacent normal and/or dysplastic mucosa, 30 associated metastases, and 12 recurrences were immunostained for CD44s, -v3, -v4, -v5, -v6, -v7, -v9, E-cad, and beta-cat. In non-neoplastic epithelium, all molecules investigated were constitutively expressed in the basal layers. In the majority of dysplasias, immunoreactivity for all adhesion molecules was increased, but there was restricted loss for CD44s, E-cad, and beta-cat in a few cases. In carcinomas, a striking accumulation of CD44s, v3, v4, v9 and a loss of E-cad/beta-cat were observed at the invasive tumour front. In metastases and recurrences, besides a loss of CD44s, v4, v7, and E-cad, a significant increase of v9 was recorded, whereas CD44v5 and v6 remained unchanged. Clinically, reduced expression of CD44v3, E-cad, and changes of CD44v9 phenotype within the primary tumours correlated significantly with poor prognosis; decreased beta-cat expression was a predictive marker for nodal metastases. These findings indicate that there is some perturbed expression of adhesion molecules during the stepwise course of oral carcinogenesis and tumour progression. Distinct phenotypic alterations project poor prognosis, while others predict metastasis. Some of these restricted molecular changes may serve as potential targets for future antibody-based tumour therapy., (Copyright 2002 John Wiley & Sons, Ltd.)

Background: Deranged expression and function of the E-cadherin/beta-catenin (E-cad/beta-cat) complex and the epidermal growth factor receptor (EGFR) have been implicated in the development and progression of carcinomas., Methods: To estimate the role of these molecules in oral cancer, we investigated 75 primary oral squamous cell carcinomas (OSCCs) with adjacent normal and/or dysplastic mucosa, 30 paired metastases and 12 recurrences by immunohistochemistry., Results: All three molecules were constitutionally expressed in the basal/parabasal layers of tumour adjacent 'normal' epithelium, in contrast to a significant increase of EGFR and heterogeneous expression of E-cad/beta-cat in dysplasia. In OSCCs, over-expression of EGFR correlated significantly with lower tumour grade and poor prognosis, loss of E-cad was a significant marker for shortened survival, reduced beta-cat staining was a predictive marker for lymph node metastasis., Conclusions: There is a perturbance in intercellular adhesion molecules and EGFR expression/function in oral cancer with major clinical impact. E-cad and beta-cat seem to inhibit EGFR to enhance the progression of OSCCs.