Prognostic value of immunoexpression of CCR4, CCR5, CCR7 and CXCR4 in squamous cell carcinoma of tongue and floor of the mouth.

BACKGROUND: Diverse studies have evidenced that chemokines can play a critical role in pathogenesis of oral squamous cell carcinoma (SCC). The main chemokines involved in oral carcinogenesis, tumor invasion and metastasis are CCR4, CCR5, CCR7 and CXCR4, and our aim was to evaluate the prognostic value of the immunoexpression of these chemokines in SCC of tongue and floor of the mouth. MATERIAL AND METHODS: A retrospective descriptive study of the immunohistochemical expression of CCR4, CCR5, CCR7 and CXCR4 in paraffin-embedded samples of 124 patients with SCC of the tongue and floor of the mouth was performed, considering 98 cases from Brazil and 26 cases from Chile. Associations between variables were analyzed using chi-square test. Survival curves were performed using the Kaplan-Meier method and compared with long-rank test. For multivariate survival analysis, the Cox hazard model was established. The level of significance established was p≤0.05. RESULTS: The statistical analysis showed that samples with well or moderate WHO model differentiation (p=0.001) and a high expression of CCR5 (p=0.05) were significantly associated with a higher disease specific survival, which were also observed in Cox's multivariate analysis (p=0.01). A higher expression of CCR7 (p=0.01) interfered significantly in disease-free survival in univariate analysis and in Cox's multivariate analysis (p=0.05). CONCLUSIONS: These results support additional evidence, showing that chemokine receptors CCR5 and CCR7 are helpful as biomarkers of poor prognosis in patients with SCC of the tongue and floor of the mouth.

Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an extended family.

BACKGROUND: The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. MATERIAL AND METHODS: To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. RESULTS: The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. CONCLUSIONS: These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. CLINICAL RELEVANCE: This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS1.

Cleidocranial dysplasia: oral features and genetic analysis of 11 patients.

BACKGROUND: Cleidocranial dysplasia (CCD) is a dominantly inherited autosomal disease characterized by typical bone defects including short stature, persistently open or delayed closure of the cranial sutures, and hypoplastic or aplastic clavicles. Oral features are frequent and include supernumerary teeth, delayed eruption or impaction of the permanent teeth, and malocclusion. Heterozygous mutations in RUNX2 gene, which encodes a transcription factor essential for osteoblast differentiation, were identified as the etiological cause of CCD. OBJECTIVE AND METHODS: Herein, we performed physical and radiographic examination and screening for RUNX2 mutations in 11 patients from five families with CCD. RESULTS: All patients demonstrated the classical phenotypes related to CCD. Families whose affected members had several dental alterations such as multiple impacted and supernumerary teeth demonstrated heterozygous missense mutations (R190Q and R225Q) that impair the runt domain of RUNX2. On the other hand, CCD patients from families with low frequency of dental abnormalities showed no mutation in RUNX2 or mutation outside of the runt domain (Q292fs→X299). CONCLUSION: The current findings suggest a correlation between dental alterations and mutations in the runt domain of RUNX2 in CCD patients. Further clinical and genetic studies are needed to clarify the relationship between phenotypes and genotypes in CCD and to identify other factors that might influence the clinical features of this uncommon disease.

Idiopathic gingival fibromatosis: description of two cases.

Gingival fibromatosis is an enlargement localized or generalized of the gingival tissue characterized by an expansion and accumulation of the connective tissue, predominantly type I collagen, with occasional presence of increased number of cells, supposed fibroblastic proliferation. Gingival fibromatosis can be induced as a side effect of systemic drugs, such as phenytoin, cyclosporin, and nifedipine, or due to hereditary factors. However, in some cases, the gingival overgrowth is idiopathic. This paper reports two cases of idiopathic gingival fibromatosis and discusses the diagnosis, histopathological features, treatment and immunohistochemical evaluation of myofibroblasts of this condition. The tissues removed were fixed in formalin, and sections used for hematoxylin and eosin and Masson tricromic stain. To determine the presence of myofibroblasts, we performed immunohistochemistry against a-SMA protein. Histological examination revealed epithelial hyperplasia with long rete pegs and increase in the dense fibrous connective tissue. The Masson tricromic stain revealed wide bundles of collagen strongly stained. It was showed negative labeling to a-SMA. These results strongly suggest that myofibroblasts are not involved in gingival overgrowth in the cases of IGF reported. Future studies will be necessary to determine the pathogenesis of idiopathic gingival fibromatosis.

Lack of association between IRF6 polymorphisms (rs2235371 and rs642961) and non-syndromic cleft lip and/or palate in a Brazilian population.

BACKGROUND: Interferon regulatory factor 6 (IRF6) gene has emerged as a potential susceptibility gene for non-syndromic cleft lip and/or palate (NSCL/P) in different populations. The aim of this study was to determine the association of IRF6 rs2235371 and rs642961 polymorphisms with NSCL/P in a Brazilian population. METHODS: Two hundred and twenty-eight patients affected by NSCL/P and 126 healthy individuals were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: Overall genotype distributions of rs2235371 and rs642961 polymorphisms were as expected by Hardy-Weinberg equilibrium test. The rs2235371 polymorphic genotype GA was identified in 10.1% of the patients with NSCL/P and in 10.3% of the control group, revealing no statistical difference. Similarly, the frequency of rs642961 minor genotypes (GA and AA) was quite similar between control group (28.6%) and NSCL/P group (25.4%), without significant difference. CONCLUSION: Our findings are consistent with a lack of involvement of IRF6 rs2235371 and rs642961 polymorphisms in the NSCL/P pathogenesis in the Brazilian population.