p63 expression correlates with pathological features and biological behaviour of odontogenic tumours.
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A total of 123 cases of odontogenic cysts, distributed as follows: 30 follicular (FC), 35 radicular (RC), 53 keratocysts, 1 glandular odontogenic and 4 calcifying odontogenic cysts, were analysed by immunohistochemistry for expression of p63, a component of p53 protein family. In RCs p63 positivity was not only in basal and parabasal layers but also in the intermediate layer and about 1/3 of cases displayed a percentage of stained cells comprised between 0 and <5%, and about 2/3 between >5% and <50%. In FCs positivity was confined to basal and parabasal layers of the epithelium and in the majority of FCs the stained cells were comprised between 0 and <5%. OKCs displayed the most intense and diffuse p63 labeling. In conclusion, these data suggest that p63 expression may be useful to identify cysts type with more aggressive and invasive phenotype supporting the hypothesis of a suprabasal proliferative compartment in OKCs.
AIM: To determine whether or not matrix metalloproteinase 13 (MMP-13) is present in periapical granulomas with and without epithelium. METHODOLOGY: Seventeen open periapical granulomas of pulpal origin (seven lesions without epithelium and 10 with proliferating epithelium) were fixed in formalin and then embedded in paraffin prior to being processed for immunohistochemical analysis. A monoclonal antibody against human MMP-13 was used to evaluate MMP-13 expression. Immunocomplexes were subsequently treated with the secondary antibody and then detected by means of streptavidin peroxidase. Immunoreactivity was visualized by development with 3,3'-diaminobenzidine. RESULTS: An immunopositive cytoplasmatic reaction for MMP-13 was observed in all the specimens, although the immunostaining by anti-MMP-13 antibody was heterogeneous and its levels varied according to histopathological findings. In periapical lesions without epithelium MMP-13 immunolabelling was detected in a few fibroblast-like cells, and in some plasma cells within the granulomatous tissue. A clear upregulation of MMP-13 expression was detected in periapical lesions with epithelium, especially in small island and thin strands of epithelium. CONCLUSIONS: The expression pattern of MMP-13 demonstrates that it is involved in the conversion of a periapical granuloma with epithelium into a radicular cyst. This property is related to the ability of MMP-13 to influence not only the migration of epithelial cell but also the invasion of granulomatous tissue.
The aim was to investigate the relationship between the vertical craniofacial morphology and the sagittal path of mandibular movements. The study was carried out in 40 subjects who were free of temporo-mandibular disorders. Mandibular movements and maximal jaw opening (MO) were recorded by means of a jaw tracking device. The opening-closing angle (OCA) was defined as the angle between the horizontal plane and the opening-closing path of movements. Vertical craniofacial morphology was assessed on prophile cephalograms by means of the Frankfort Mandibular Plane Angle (MP). The OCA did not differ between males and females (P>0.05). OCA and MP were negatively correlated (r=-0.62; P<0.001). MO was significantly greater in males that in females (P<0.05). MO was negatively correlated to MP (-0.44<r<-0.49; P<0.05). The findings suggest that the low-angle subjects exhibit a more vertical path of the mandibular movements than that of high-angle subjects. Differences in the sagittal path of jaw movements may be partly ascribed to anatomical factors.
27 kDa Heat shock protein (Hsp27), which is also identified as p29 estrogen-receptor associated protein, plays a crucial role in specific growth stages. It also seems to be involved in the balance between differentiation and apoptosis. To determine whether Hsp27 is involved during craniofacial development and odontogenesis, its expression was studied through immunohistochemistry of developing jaw bone as well as the odontogenesis of heads from human fetuses. Formalin-fixed paraffin-embedded specimens of 7 human fetuses (3 female, 4 male), obtained from miscarriages occurring between the 9th and 16th weeks of pregnancy, were examined by using a monoclonal antibody against Hsp27. Staining intensity (weak, +; moderate, ++; strong, +++) was evaluated semiquantitatively. The sample slice was cut through a coronal plane, which included eyes, nasal cavities, tongue, and primitive dental lamina with tooth germs. A transient and spatially restricted expression of Hsp27 in developing human jaw bones and teeth was observed. Osteoblasts around the uncalcified bone matrix showed Hsp27 immunoreaction products (+++), whereas osteocytes were not immunolabeled. In mandibular condyle, immunolabeling was restricted to hypertrophic chondrocytes (++). In developing tooth germs, Hsp27 immunostaining was detected throughout the bud (+++). At the early cap stage, a strong immunolabeling for Hsp27 was seen in the dental lamina (+++), and a moderate staining was seen in the outer dental epithelium (++). At the late cap stage, Hsp27 expression was detected in the outer dental epithelium (++) as well as in the cells of the future stellate reticulum (++). The spatiotemporal-restricted expression of Hsp27 in craniofacial bones during development suggests that this protein could be involved in the balance between differentiation and apoptosis, by modulating the viability of osteoblasts and chondrocytes. The specific regional and temporal expression patterns of Hsp27 during tooth development sustains that this small Hsp might be related to the morphogenesis and cytodifferentiation processes of tooth germs.
UNLABELLED: HSP27 belongs to the Heat shock protein (HSP) family, which plays essential functions in cells under physiological conditions and prevents stress-induced cellular damage. The aim of this study was to investigate the biological role of HSP27 in oral tumorigenesis. MATERIALS AND METHODS: Seventy-nine cases of oral squamous cell carcinoma and 10 cases of normal mucosa were analysed for HSP27 expression by immunohistochemistry. Moreover, the western blot analysis was performed on two cases of normal mucosa and five cases of OSCC. RESULTS: Normal oral mucosa showed a suprabasal expression of HSP27. Twenty-four cases of SCC (30.7%) showed a diffuse staining for HSP27, and 48 cases (60.3%) showed instead a decrease in staining, which was diffuse, homogeneous, or with alternation of positive and negative areas in a single tumor ("mosaic" pattern). Only 7 cases of OSCC (7.5%) were completely negative for HSP27. Frequency of lymph node metastases was higher in HSP27-negative tumours (3/7, 42.8%) than in HSP-reduced (16/48, 33.3%) or positive ones (5/26, 19.2%). Regard staging, stages I and II had a higher score than stages III and IV (stage I > stage II > stage III > stage IV). There was also a statistically significant correlation between HSP27 expression and grade: HSP27 expression was reduced in poorly differentiated tumours (P < 0.05). When analysed for prognostic significance, patients with negative/reduced HSP27 expression had poorer survival rates than the group with positive HSP27 expression (P < 0.05). The statistical analysis of these findings showed no significant correlation between HSP27 expression, sex, and tumour size. CONCLUSION: Cases with reduced expression were more aggressive and poorly differentiated. These data suggest that HSP27 expression may be useful in order to identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype providing novel diagnostic and prognostic information on individual patient survival with oral cancers.
Oral-facial-digital syndrome type I (OFDI) is a congenital X-linked dominant disorder characterized by anomalies of the oral cavity, face and digits sometimes associated to cerebral malformations and polycystic kidney disease. The gene, responsible for this syndrome, is ofd1. Clinically it is seen only in females. Lesions of the mouth include median pseudoclefting of the upper lip, clefts of the palate and tongue, and dental anomalies (missing or supernumerary teeth, enamel hypoplasia, and teeth malpositions). Dysmorphic features affecting the head include hypertelorism, frontal bossing, micrognathia, facial asymmetry and broadened nasal ridge. The digital abnormalities are syndactyly, clinodactyly, brachydactyly and, rarely, pre or post-axial polydactyly. Less frequently ex-pressed phenotypic anomalies include skin milia, alopecia, deafness and trembling. Sometimes the diagnosis of OFDI can be difficult because there is an overlap with other types of oral-facial-digital syndromes. A sporadic case of OFDI, with 7 lower incisors, both in the primary and permanent dentition, is reported. This dental anomaly is very unusual because in literature only supernumerary cuspids are reported. In the light of this case, the authors discuss the oral phenotypic expression of ofd1 gene and its role in human odontogenesis.
A high density of blood vessels is found in specimens of temporomandibular joint (TMJ) disc at any stage of internal derangement of the joint, but the factors responsible for angiogenesis in the disc have not been described. The purpose here was to investigate, in human TMJ discs, the expression of vascular endothelial growth factor (VEGF), a multifunctional cytokine that contributes to angiogenesis. Specimens, free of significant morphological alterations and with varying degrees of disc tissue degeneration/regeneration, were studied by immunohistochemistry for VEGF in order to correlate immunohistochemical with histopathological findings. In normal discs and discs with minor pathological changes, fibroblast-like cells, fibrochondrocytes and chondrocyte-like cells were either not or only weakly immunostained by VEGF antibody. In disc specimens from internal derangement of the TMJ with significant tissue degeneration/regeneration, VEGF was consistently expressed. In these specimens, immunoreaction products for VEGF were observed both in the disc and in the endothelial cells of newly formed vessels. This VEGF immunolocalization is consistent with the stimulation of angiogenesis and the morphogenesis and differentiation of chondrocytes. Therefore VEGF expression by disc chondrocyte-like cells might reflect the action of the cytokine as an inducer of angiogenesis and as an autocrine signal for cells of the chondrogenic lineage.
Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is a multifunctional cytokine. It is overexpressed in several conditions, which are characterized by vascular hyperpermeability and angiogenesis. In this investigation, we have evaluated the possibility that VEGF/VPF could be expressed in periapical lesions. We studied 17 periapical granulomas and 6 periapical cysts by immunohistochemistry. An immunopositive reaction for VEGF/VPF was observed in all 23 periapical lesions; however, the intensity of immunostaining by anti-VEGF antibody varied according to histopathological findings. In periapical granulomas without epithelium, almost all of the inflammatory cells were immunoreactive to anti-VEGF/VIP antibody. In periapical granulomas, which had rests of Malassez in them, some inflammatory cells were stained. On the other hand, epithelial cells always were stained by VEGF/VPF antibody, both in periapical lesions with epithelium and in radicular cysts. This study demonstrated that periapical lesions express VEGF/VPF, although with some differences in cell immunolabeling, which correlated to the lesions' stages of development. Initially, VEGF/VPF would assure angiogenesis and vascular hyperpermeability, resulting in accumulation of inflammatory cells, later it could be involved in cyst fluid accumulation. We hypothesize, therefore, that VEGF/VPF expression plays an important role in the pathogenesis of periapical granulomas and enlargement of radicular cysts by several mechanisms.
Survivin is a recently described apoptosis inhibitor selectively over-expressed in most tumors. Immunohistochemistry was used to investigate a potential role of survivin as an early predictor of malignant transformation in precancerous and cancerous lesions of the oral cavity. Survivin was present in 10/30 cases (33%) of oral precancerous lesions without malignant progression, and in 15/16 cases (94%) of oral precancerous lesions evolved into full-blown squamous cell carcinoma. Tumors that progressed from these precancerous lesions retained widespread survivin positivity (100%). Variations among group means were highly statistically significant (p < 0.001). No significant correlation was found between survivin expression and the degree of dysplasia. High expression of cytoplasmic/nuclear survivin is an early event during oral carcinogenesis and may provide a useful tool for the identification of precancerous lesions at higher risk of progression into invasive carcinoma.
The expression of vimentin and alpha-smooth muscle (alpha-SM) actin was examined in 10 human temporomandibular joint (TMJ) disc samples, with internal derangement and in two control specimens, in order to evaluate the phenotypic characteristics of TMJ disc cells in relationship to histological findings. This was accomplished by means of monoclonal antibodies specific for vimentin and alpha-SM actin and immunocytochemical technique. The study, revealed that every disc cell constantly expressed vimentin. Scattered alpha-SM actin positive cells could be appreciated in normal TMJ discs and tissues with minor pathological findings. In TMJ discs with severe alterations, i.e. tears and clefts, almost fibroblast-like cells, fibrochondrocytes and chondrocyte-like cells were strongly immunolabelled by anti-alpha-SM actin antibody. According to these findings it can be assumed that vimentin is expressed by all disc cell populations and it appears not to be influenced by any disease condition of the disc; on the other hand the up-regulation alpha-SM actin immunolabelling seems to be correlated to histopathological findings of tears and clefts. Cells, with a contractile phenotype, close to such defects, could be involved in disc tissue contraction and repair. The plasticity of disc cell populations which evolve towards a different phenotype when subjected to action of macro- and micro-environmental factors is also supported.
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In this report we present a subject affected by nevoid basal cell carcinoma syndrome (NBCCS), showing also bilateral mandibular coronoid processes hyperplasia, a hitherto unreported association. Our observation of bilateral hyperplasia of the mandibular coronoid processes in a boy with NBCCS may prompt a retrospective and prospective review of other patients affected by this syndrome in order to establish if this anomaly is part of it.
PURPOSE: This study investigated histochemically the elastic fibers in human temporomandibular joint (TMJ) discs with varying degrees of tissue degeneration/regeneration to determine whether there are differences that correlate with the histologic findings. MATERIALS AND METHODS: Ten diseased human TMJ discs and 2 control specimens were studied histochemically by staining with Weigert's resorcin-fuchsin after oxidation with peracetic acid. This technique selectively stains elastic, elaunin, (pre-elastic), and oxytalan fibers. RESULTS: In TMJ discs with an abnormal collagen fiber arrangement, an increased number of oxytalan fibers could be observed, contrary to discs with scar-like tissue transformation in which oxytalan fibers were decreased in number. In discs showing tears and clefts, the oxytalan fibers run perpendicular to the defects, whereas elaunin and elastic fibers were mainly circumferentially arranged. In discs with chondroid metaplasia, elastic, elaunin, and oxytalan fibers were extensively detected. CONCLUSIONS: It is hypothesized that the elastic, elaunin, and oxytalan fibers found in severely damaged discs appear to ensure biomechanical compliance by reinforcing regions devoid of collagen bundles and thus function as shock absorbers of stretch and compression.
Heat shock protein (HSP) 27 is a member of the small HSP family that plays a part in the regulation of epithelial cell growth and differentiation, wound healing, apoptosis and cell protection against inflammatory cytotoxicity mediators. Thus the expression of HSP27 was investigated immunohistochemically in periapical granulomas with epithelial rests of Malassez and in radicular cysts. Anti-HSP27 mouse monoclonal antibody and peroxidase-labeled streptavidin-biotin standard technique were used to study the expression of HSP27. Proliferating epithelial cell rests, and islands of epithelium and epithelial lining of microcysts strongly reacted throughout all layers, whereas radicular cysts epithelial lining presented mainly a moderate suprabasal staining pattern. However both the proliferating epithelial cell rests and the radicular cysts shared an over-expression of HSP27 immunostaining intensity in coincidence with the presence of local infiltration of immune cells. HSP27 may play several roles in periapical lesions that include contributing to the migration of epithelial cell rests and an increased resistance both to necrotic and apoptotic cell deaths.
Coronary artery aneurysms are often incidental findings during coronary angiography; they are mostly secondary to atherosclerosis or vasculitis, they are rarely congenital. Right coronary circumflex and anterior descending arteries are usually involved but only few cases of aneurysms of left main coronary artery are reported. A case of coronary artery aneurysms is described involving left main, right and anterior descending coronary arteries, probably secondary to atypical Kawasaki disease in a 33 years old man with acute myocardial infarction.