TWIST1 regulates proliferation, migration, and invasion and is a prognostic marker for oral tongue squamous cell carcinoma.

BACKGROUND: Epithelial-mesenchymal transition is one of the main mechanisms for tumor progression and metastasis. Transcription factors such as TWIST1 are key regulators of the epithelial-mesenchymal transition and are regarded as potential therapeutic targets for the treatment of cancer. The purpose of this study was to examine TWIST1 as a possible epithelial-mesenchymal transition-related prognostic biomarker in oral epithelial dysplasia and oral tongue squamous cell carcinomas, as well as the biological behavior of TWIST1-silencing in oral tongue squamous cell carcinomas cell lines. METHODS: Immunohistochemical analysis of TWIST1, E-cadherin, and N-cadherin was carried out in 47 samples representing oral epithelial dysplasia and 41 oral tongue squamous cell carcinomas. The suppression of TWIST1 expression was performed using shRNA-expression vectors in HSC-3 and SCC-9 cells to investigate in vitro the impact of TWIST1 on proliferation, apoptosis, viability, migration, and invasion of SCC-9 and HSC-3 cells. RESULTS: The expression of nuclear TWIST1 was significantly higher in oral tongue squamous cell carcinomas than in oral epithelial dysplasis (p < 0.0001), whereas TWIST1 in the cytoplasm was more expressed in oral epithelial dysplasis (p = 0.012). The high cytoplasmic expression of TWIST1 was significantly associated with shortened overall survival (p < 0.05), and increased nuclear TWIST1 expression was significantly related to high risk of recurrence (p = 0.03). Knockdown of TWIST1 in oral tongue squamous cell carcinomas cells induced the expression of E-cadherin and inhibited N-cadherin, which were followed by decreased proliferation, migration, and invasion. CONCLUSIONS: Our research suggests that TWIST1 is linked to the development of oral tongue carcinogenesis and may be used as a prognostic indicator and therapeutic target for oral tongue squamous cell carcinomas patients.

Comparison of immunoexpression of dendritic cells, mast cells and blood vessels in periodontal disease between adults and elderly.

OBJECTIVE: The aim of this study was to compare, in adults and elderly individuals, the immunoexpression of immature and mature dendritic cells (DCs), mast cells, and blood vessels in healthy and diseased gingival tissues. MATERIALS AND METHODS: The expressions of immunohistochemical markers, including CD1a (immature dendritic cells), CD83 (mature dendritic cells), tryptase (mast cells) and CD34 (blood vessels), were analyzed in gingival biopsies from elderly (n = 27) and adult (n = 127) patients presenting health, gingivitis and periodontitis. Positive cells for each specimen and marker were counted. RESULTS: There were no differences in the immunostaining of DCs, mast cells and the amount of blood vessels among gingival biopsies with health, gingivitis and periodontitis in adult and elderly subjects (p > 0.05). Immature DCs were more frequent in tissues with gingivitis and periodontitis in elderly patients, when compared to adults (p < 0.05). Furthermore, degranulated mast cell counts were higher, whereas the number of microvessels was lower in gingivitis in the elderly, when compared to adults (p < 0.05). CONCLUSIONS: Diseased periodontal sites in the elderly present an overall significant overexpression of immature DCs and degranulated mast cells, in relation to those of adults. Furthermore, gingivitis in elderly is associated with decreased microvessel growth. These immunoinflammatory differences between elderly and adults may have implications in periodontal tissue breakdown in the late adulthood. Further studies should be performed to elucidate this hypothesis. CLINICAL RELEVANCE: Understading the relationship between aging and changes in immune cells during periodontal inflammation may lead to therapeutic targets for the future management of periodontal diseases.

Sociodemographic and clinical characterization of cases of 1,103 non-syndromic and 66 syndromic odontogenic keratocyst: a Brazilian multicenter study.

OBJECTIVES: This multicenter study aimed to evaluate cases of non-syndrome and syndromic odontogenic keratocyst, as well as cases of recurrence within these two groups. METHODS: This descriptive, analytical, retrospective cross-sectional study evaluated the sex, age and presence of multiple lesions in 1,169 individuals seen at 10 Brazilian oral and maxillofacial pathology centers. Of these, 1,341 odontogenic keratocysts were analyzed regarding clinical diagnosis, size, site, imaging appearance, signs and symptoms, type of biopsy, treatment, and recurrence. RESULTS: There was a similar distribution by sex. The median age of non-syndromic and syndromic patients was 32 and 17.5 years, respectively. The posterior mandible was the site most affected by small and large lesions in both groups and in recurrent cases. Unilocular lesions were more frequent, also in recurrent cases. Mainly small lesions showed this imaging appearance. Signs and symptoms were absent in most cases. Conservative treatment was the most frequent modality in all age groups, regardless of the patient's condition and recurrence. Recurrences were uncommon. CONCLUSION: This study showed a higher frequency of non-syndromic keratocysts in the population. Clinicopathological features related to the involvement of multiple sites, age, and recurrence may differ between syndromic and non-syndromic cases. Furthermore, we found an association between lesion size and some clinical features and between the time interval to recurrence and the syndromic spectrum. CLINICAL RELEVANCE: To contribute to a better understanding of the distribution and association between clinical, imaging, and sociodemographic characteristics in each spectrum of the lesion.

Histopathologic grading and its relationship with outcome in oral tongue squamous cell carcinoma.

BACKGROUND: Histopathologic grading has been routinely used as a complement for clinical staging in the prognostication of patients with oral tongue squamous cell carcinoma (OTSCC). However, this subject remains contentious because there is no universally accepted grading system. OBJECTIVES: This study compared the prognostic significance of four histopathologic grading systems in 80 cases of oral tongue squamous cell carcinoma (OTSCC). METHODS: Clinical and follow-up information of the patients were obtained from medical records. Histopathologic malignancy grading of the tumor invasive front, Histologic risk assessment (HRA), World Health Organization (WHO) grading system, and Budding and Depth of invasion (BD) model were evaluated in the surgical specimens. RESULTS: The HRA, histopathologic malignancy grading and WHO systems did not predict survival. Patients with larger tumor size [Hazard ratio (HR): 2.38; 95% confidence interval (CI): 1.07-5.27; P = 0.026] and patients with BD model high-grade tumors (HR: 2.99; 95% CI: 1.03-8.68; P = 0.034) were significantly associated with a poor 5-year overall survival rate. In the multivariate analysis, tumor size was identified as the only significant independent prognostic factor (HR: 2.23; 95% CI: 1.00-4.99; P = 0.050). None of the grading systems studied was associated with 5-year disease-free survival rates. CONCLUSIONS: BD model was the only histopathologic grading system associated with the outcome of patients with OTSCC, indicating its potential value as an effective tool for the prognostication of OTSCC.

Stanniocalcin 2 contributes to aggressiveness and is a prognostic marker for oral squamous cell carcinoma.

Stanniocalcin 2 (STC2), a glycoprotein that regulates calcium and phosphate homeostasis during mineral metabolism, appears to display multiple roles in tumorigenesis and cancer progression. This study aimed to access the prognostic value of STC2 in oral squamous cell carcinoma (OSCC) and its implications in oral tumorigenesis. STC2 expression was examined in 2 independent cohorts of OSCC tissues by immunohistochemistry. A loss-of-function strategy using shRNA targeting STC2 was employed to investigate STC2 in vitro effects on proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition (EMT) and possible activation of signaling pathways. Moreover, STC2 effects were assessed in vivo in a xenograft mouse cancer model. High expression of STC2 was significantly associated with poor disease-specific survival (HR: 2.67, 95% CI: 1.37-5.21, p = 0.001) and high rate of recurrence with a hazard ratio of 2.80 (95% CI: 1.07-5.71, p = 0.03). In vitro downregulation of STC2 expression in OSCC cells attenuated proliferation, migration and invasiveness while increased apoptotic rates. In addition, the STC2 downregulation controlled EMT phenotype of OSCC cells, with regulation on E-cadherin, vimentin, Snail1, Twist and Zeb2. The reactivation of STC2 was observed in the STC2 knockdown cells in the in vivo xenograft model, and no influence on tumor growth was observed. Modulation of STC2 expression levels did not alter consistently the phosphorylation status of CREB, ERK, JNK, p38, p70 S6K, STAT3, STAT5A/B and AKT. Our findings suggest that STC2 overexpression is an independent marker of OSCC outcome and may contribute to tumor progression via regulation of proliferation, survival and invasiveness of OSCC cells.

Association of PON1, TNF-α and TGF-ß gene polymorphisms with prognosis in oral and oropharyngeal squamous cell carcinoma.

OBJECTIVE: The oral and oropharyngeal squamous cell carcinoma (OOSCC) accounts for 90-95% of tumours in the oral cavity. Single nucleotide polymorphism (SNP) in the coding region of PON1, tumour necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-ß) have been associated with to development of different cancers. Our aim was to investigate the prognostic value of PON1 (rs854560 and rs662), TNF-α (rs1800629 and rs361525) and TGF-ß (rs1800469) SNPs in OOSCC. MATERIALS AND METHODS: We genotyped 163 OOSCC patients and 146 patients from group of control for PON1 (rs854560 and rs662), TNF-α (rs1800629 and rs361525) and TGF-ß (rs1800469) SNPs by real-time polymerase chain reaction (PCR). RESULTS: TNF-α (rs1800629) GG genotype was significantly more frequent in intraoral lesions and clinical stages III and IV, while the polymorphic AA genotype in lip lesion and clinical stages I and II. Moreover, TGF-ß (rs1800469) AG and AA genotypes were significantly more frequent in larger tumours (T3 e T4). TNF-α (rs1800629) AG genotype had poor survival and patients carrying the PON1 (rs662) TT genotype tended to poor survival. CONCLUSIONS: Results suggest that the rs1800629 and rs1800469 could exert influence in the more aggressive behaviour of OOSCC and the genotypes AG of rs1800629, and TT of rs662 could be markers with prognostic value in OOSCC.

Neurofibromas of the oral and maxillofacial complex: A 48-year retrospective study.

Neurofibromas are benign neoplasms of the peripheral nerve sheath, characterized by the proliferation of Schwann cells, perineural cells and endoneural fibroblasts. Their occurrence in the oral and maxillofacial complex is uncommon. This study aimed to evaluate the clinical and histopathological characteristics of neurofibromas of the oral and maxillofacial complex excised at our institution over a 48-year period. Using light microscopy, two previously trained oral pathologists re-evaluated all hematoxylin and eosin slides. From a total of 15,375 cases diagnosed at a referred Oral Pathology Service, 24 cases were diagnosed as neurofibromas. Eighteen neurofibroma patients were female, with a mean age of 39.1 years. Three patients presenting neurofibromas exhibited neurofibromatosis type I. Clinically, most of the lesions presented as asymptomatic nodules, and the most frequent sites were the tongue (n = 6; 25.0%), gingiva (n = 6; 25.0%) and intraosseous maxillary bone region (n = 3; 12.5%). Histopathologically, the lesions were predominantly well delimited, exhibiting interlocking bundles of spindle-shaped cells that usually displayed wavy nuclei, associated with delicate collagen fibers. Thus, knowledge of their clinical and histopathological features by dentists and oral pathologists is essential for the correct diagnosis of these lesions.

Immunohistochemical expression of TFIIH and XPF in oral tongue squamous cell carcinoma.

PURPOSE: The query for biomarkers that indicate tumor aggressiveness and the host's response to treatment is still one of the leading aims of cancer research. To investigate a possible role for DNA nucleotide repair proteins in oral cancer behavior, this study evaluated the immunoexpression of the proteins TFIIH and XPF and its association with clinical, histological, and survival parameters in oral tongue squamous-cell carcinoma (OTSCC). METHODS: TFIIH and XPF immunoexpressions were evaluated in 82 cases of oral tongue squamous-cell carcinoma. Tumor budding and depth of invasion were assessed for histopathological grading (BD model). RESULTS: Tumor cells exhibited high expression of TFIIH and XPF, which was associated to nodal status; both proteins were not associated with other clinical parameters, histopathological grading or survival. Tumor size, nodal status, tumor staging, and depth of invasion > 4 mm were significantly associated to disease-specific survival. CONCLUSIONS: We have demonstrated that the overexpression of TFIIH correlates positively with node metastasis, while XPF correlates negatively with node metastasis; therefore, the expression of XPF and TFIIH had a potential value for predicting the progression of OTSCC patients.

The occurrence and pattern of head and neck sarcomas: a comprehensive cancer center experience.

PURPOSE: This study aimed to analyze the demographics, clinicopathological, treatment, and survival characteristics of head and neck sarcomas diagnosed in a reference center in the Brazilian Northeast. MATERIALS AND METHODS: This retrospective cohort study reviewed the clinical records of patients with head and neck sarcomas. Epidemiologic data consisted in clinical location, age, gender, histopathological diagnosis, clinical TNM staging and treatment. Outcome variables were local recurrence and survival. The statistical analyses were performed by a binary logistic regression analysis. The survival analysis was assessed through the Kaplan-Meier curve. RESULTS: Sixty-nine patients with head and neck sarcomas (male 39; female 30) were analyzed. The most common histologic subtypes were rhabdomyosarcoma, dermatofibrosarcoma, and pleomorphic sarcoma. The mean age of the patients at the time of diagnosis was 38.1 years old. A total of 31 patient died (sarcoma-related death) up to the end of the follow-up, with a mean follow-up rate of 1.63 years. A multivariate analysis revealed that anatomical site, treatment modality, histopathological diagnosis, and clinical stage of the disease were associated with specific survival, reaching statistical significance. CONCLUSION: This study demonstrates the impact of important clinical-pathological parameters on the overall prognosis of head and neck sarcomas.

Extracapsular invasion: A potential prognostic marker for Carcinoma ex-pleomorphic adenoma of the salivary glands? A Systematic Review.

BACKGROUND: The aim of the present study was to integrate available data published in the literature on extracapsular invasion in cases of CXPA that correlated findings with the prognosis of analysed patients. METHODS: An electronic search was carried out at the MEDLINE/PubMed, EMBASE and Cochrane Collaboration Library databases. Articles that assessed the relationship between extracapsular invasion and survival of patients diagnosed with CXPA were selected for the systematic review. Quality assessment was performed, in duplicate, for each eligible study by independent reviewers who used the operationalized prognostic biomarker reporting the REMARK guidelines. RESULTS: Eight published articles met all the inclusion criteria and were selected. Extracapsular invasion was evaluated in all selected studies and was correlated with clinical and pathological parameters. Recurrence and death due to the neoplastic process became a frequent finding in cases of tumours with extracapsular invasion >1.5 mm, being an important cut-off point in the prognostic analysis of cases diagnosed as CXPA. CONCLUSIONS: This systematic review demonstrates the importance of evaluating extracapsular invasion in cases diagnosed as CXPA, considering that tumours with invasion >1.5 mm, regardless of histopathological subtype, are associated with a worse prognosis. It is important to analyse the extracapsular invasion, especially as an auxiliary method to assess the prognosis of cases diagnosed in the initial clinical stages, thus identifying the possible biological behaviour of the neoplastic process and guiding the most appropriate patient management.

Potential role of Hedgehog signaling pathway and myofibroblastic differentiation in central giant cell granuloma-A preliminary study.

OBJECTIVE: This study investigated components of the Hedgehog (HH) signaling pathway (SHH, GLI1), cyclin D1, and smooth muscle actin (SMA) in central giant cell granulomas (CGCG). The relationship between these proteins and myofibroblasts was also studied. MATERIAL AND METHODS: Twelve cases of non-aggressive CGCG and 11 cases of aggressive CGCG were studied using immunohistochemistry for SHH, GLI1, Cyclin D1, and SMA. RESULTS: Associations between all proteins in non-aggressive and aggressive CGCG were not significant (P > .05). All cases of CGCG showed significantly higher expression of SMA compared with the other proteins (P < .01). A positive correlation (P = .04) was only observed between SHH and GLI1 for all cases of CGCG. Furthermore, a positive correlation between SHH and GLI1 in non-aggressive CGCG (P = .04) and between GLI1 and cyclin D1 in aggressive CGCG (P = .03) were observed. There was also a negative correlation between the expression of SHH and SMA in non-aggressive CGCG (P = .031). CONCLUSIONS: This study provided insights into the activation of the HH signaling pathway in CGCG. In addition, the activation of this pathway (SHH and GLI1) might play some role in the differentiation of stromal myofibroblasts, although these markers including Cyclin D1 and SMA do not indicate aggressiveness of the CGCG. Furthermore, this myofibroblastic differentiation process would occur at the expense of maturation of these lesions.

Acute primary actinomycosis involving the hard palate of a diabetic patient.

Actinomycosis is a relatively rare infection caused by saprophytic bacteria of the oral cavity and gastrointestinal tract that can become pathogenic. The chronic hyperglycemia of diabetes mellitus induces events that promote structural changes in various tissues and are associated with problems in wound healing. This infection remains largely unknown to most clinicians because of its different presentations, and palatal involvement is extremely rare. This report describes the case of a 46-year-old woman who was diagnosed with actinomycosis involving the hard palate. The main clinical, histopathologic, and therapeutic characteristics and differential diagnosis of actinomycosis are reviewed. To date, 3 cases of actinomycosis involving the hard palate have been reported.

Low-level laser therapy promotes proliferation and invasion of oral squamous cell carcinoma cells.

Low-level laser therapy (LLLT) has been shown to be effective in promoting cell proliferation. There is speculation that the biostimulatory effect of LLLT causes undesirable enhancement of tumor growth in neoplastic diseases since malignant cells are more susceptible to proliferative stimuli. This study evaluated the effects of LLLT on proliferation, invasion, and expression of cyclin D1, E-cadherin, ß-catenin, and MMP-9 in a tongue squamous carcinoma cell line (SCC25). Cells were irradiated with a diode laser (660 nm) using two energy densities (0.5 and 1.0 J/cm(2)). The proliferative potential was assessed by cell growth curves and cell cycle analysis, whereas the invasion of cells was evaluated using a Matrigel cell invasion assay. Expression of cyclin D1, E-cadherin, ß-catenin, and MMP-9 was analyzed by immunofluorescence and flow cytometry and associated with the biological activities studied. LLLT induced significantly the proliferation of SCC25 cells at 1.0 J/cm(2), which was accomplished by an increase in the expression of cyclin D1 and nuclear ß-catenin. At 1.0 J/cm(2), LLLT significantly reduced E-cadherin and induced MMP-9 expression, promoting SCC25 invasion. The results of this study demonstrated that LLLT exerts a stimulatory effect on proliferation and invasion of SCC25 cells, which was associated with alterations on expression of proteins studied.

Immunoexpression of RANK, RANKL, OPG, VEGF, and vWF in radicular and dentigerous cysts.

BACKGROUND: Radicular (RC) and dentigerous cysts (DC) can show a range from little to quite extensive primary/secondary inflammation and it is possible that the variation seen in the fibrous capsule of these cysts might reflect differences in the osteolytic activity. Moreover, the presence of hemorrhagic areas in the fibrous capsule of DC could also contribute to the increase in osteolytic activity. The aim of this study was to compare immunohistochemical expression of nuclear factor κappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG), vascular endothelial growth factor (VEGF) and angiogenic index in RC and DC. METHODS: These proteins were evaluated in 20 RC and DC by immunohistochemistry. Angiogenic index was determined by microvessel count (MVC) using anti-von Willebrand factor antibody. RESULTS: RANK and RANKL were higher in DC than RC in fibrous capsule. RC showed higher expression of VEGF in the epithelium and capsule. DC exhibited higher MVC than RC. CONCLUSIONS: Ours results suggest that RANK and RANKL play an important role in bone resorption in DC and the hemorrhagic areas in the capsule of DC could be explained by increased vessel's number. The higher VEGF expression in RC might be related to nature of these lesions, where the inflammatory process contributes significantly to these findings.

Immunohistochemical detection of receptor activator nuclear κB ligand and osteoprotegerin in odontogenic cysts and tumors.

PURPOSE: The aim of the present study was to compare the immunohistochemical detection of receptor activator nuclear κB ligand (RANKL) and osteoprotegerin (OPG) in radicular cysts (RCs), dentigerous cysts (DCs), solid ameloblastomas (SAs), and keratocystic odontogenic tumors (KOTs). MATERIALS AND METHODS: A total of 20 RCs, 20 DCs, 20 KOTs, 14 dental follicles (DFs), and 18 SAs were evaluated by immunohistochemistry using anti-RANKL and anti-OPG antibodies. The analysis was quantitative, and the number of positive cells was counted in 10 microscopic high-power fields (400×). RESULTS: The DFs, KOTs, and SAs showed higher expression of RANKL than did the RCs and DCs in the epithelium (P < .05). The epithelial expression of OPG was higher in the DFs, KOTs, RCs, and DCs than in the SAs (P < .05). The ratio of OPG less than RANKL was more frequent in SAs and OPG greater than RANKL in DCs (P < .05). CONCLUSIONS: Our results have shown differences in RANKL and OPG detection in the odontogenic cysts and tumors studied. The higher RANKL and lower OPG detection in SA could play a role in bone resorption, compatible with the tumor's biologic behavior.

Prognostic Significance of Histopathological Parameters for Salivary Gland Adenoid Cystic Carcinoma.

Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor that accounts for approximately 1% of all head and neck cancers. Despite its initial indolent behavior, long-term survival is poor due to locoregional recurrence in approximately 40% and distant metastasis in up to 60% of patients who undergo radical treatment. The histological parameters of ACC and the combination of these parameters in histopathological grading systems provide valuable prognostic information about the clinical course of the disease. Within this context, this review aims to analyze the impact of histopathological parameters, individual or combined in histopathological grading systems of malignancy, on ACC prognosis. Individual histopathological parameters such as solid pattern, presence of tumor necrosis, high-grade transformation, dominance of the epithelial component, presence of perineural and lymphovascular invasion, and positive surgical margins have negative impacts on the survival of patients with ACC. There are currently four histopathological grading systems for ACC; however, few studies have validated these systems and most of them explored small cohorts with short follow-up. Considering that the application of grading systems has been associated with ACC prognosis, a broader validation will allow not only their use for prognostic prediction but also assist in treatment planning.

A Systematic Review of Adenoid Ameloblastoma: A Newly Recognized Entity.

BACKGROUND: Recently, a new odontogenic tumor has been described, the so-called adenoid ameloblastoma (AdAM). The aim of this review was to determine the clinical and imaging features of AdAM and to describe its main histopathological findings. METHODS: The systematic review included published cases with a diagnosis of AdAM in the gnathic bones, which had sufficient clinical, imaging, and histopathological data to confirm its diagnosis. The following histopathological diagnostic criteria were adopted: presence of ameloblastoma-like components, duct-like structures, spiral cellular condensations, and a cribriform architecture. RESULTS: Fifteen articles, corresponding to 30 cases of AdAM, were selected. Most cases affected men (63.3%), with a slight preference for the mandible (16:14) and the posterior region of gnathic bones was the most commonly affected site. The mean age at diagnosis was 40.8 years. Clinically, the lesions usually presented as a swelling (53.3%) and, radiographically, as a well-defined radiolucency (33.4%). Surgical resection (40%) was the most frequently adopted treatment and recurrence occurred in 30% of cases. Microscopic examination showed cribriform areas in most AdAM cases (93.3%); duct-like structures and spiral cellular condensations were seen in 100% of the cases. CONCLUSION: The small number of reported cases, the existence of erroneous diagnoses, and the adoption of initial conservative management make it difficult to determine whether AdAM has a higher risk of recurrence or more aggressive biological behavior than conventional ameloblastomas.

Immunoexpression of TNF-α and TGF-ß in central and peripheral giant cell lesions of the jaws.

BACKGROUND: Peripheral giant cell lesion (PGCL) is a reactive process associated with a local irritating factor that shows low recurrence after treatment, especially if the irritating factor is eliminated. On the other hand, central giant cell lesion (CGCL) presents a variable clinical behavior ranging from slow and asymptomatic growth without recurrence to rapid, painful and recurrent growth. Our aim was to compare the immunoexpression of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-ß) in CGCL and PGCL. METHODS: Twenty CGCL and 20 PGCL were selected for analysis of the immunoexpression of TNF-α and TGF-ß in multinucleated giant cells (MGC) and mononucleated cells (MC). RESULTS: The PGCL showed lightly higher expression of TNF-α than CGCL. In comparison with PGCL, the CGCL showed higher expression of TGF-ß in MC and MGC (P < 0.05) and in total cells (P < 0.05). Significant positive correlation was found between expressions of TGF-ß and TNF-α in CGCL (P < 0.05). CONCLUSIONS: Our results suggest that, in CGCL, coordinated interactions between TGF-ß and TNF-α may be important for osteoclastogenesis and bone resorption. PGCL occasionally cause bone resorption but to a lower extent, a fact that might be explained by the lower expression of TGF-ß in these lesions.

Oral lesions in renal transplant.

To prevent rejection of kidney transplants, patients must be kept in immunosuppressive therapy for a long time, which includes the use of drugs such as cyclosporine, azathioprine, cyclophosphamide, and prednisone. The action of these drugs reduces the general immune response of transplant patients and thus increases their susceptibility to infections. Moreover, these drugs increase the potential of developing lesions. Therefore, oral hygiene in kidney transplant recipients contributes to maintenance of the transplanted organ and its function. Thus, an investigation of oral lesions could be counted as a notable work. The aim of this study was to investigate oral lesions in a group of 21 kidney transplant patients under immunosuppressive therapy attended during a 1-year period in the Nephrology Department of the Federal University of Sergipe, Brazil. Data related to sex, age, etiology of renal disease, types of renal transplant, time elapsed after transplantation, immunosuppressive treatment, use of concomitant agents, and presence of oral lesions were obtained. All patients received a kidney transplant from a living donor, and the mean posttransplantation follow-up time was 31.6 months; 71.5% used triple immunosuppressive therapy with cyclosporine A, azathioprine, and prednisone. Ten patients were also treated with calcium-channel blockers. Of the 21 transplant patients, 17 (81%) presented oral lesions. Gingival overgrowth was the most common alteration, followed by candidiasis and superficial ulcers. One case of spindle cell carcinoma of the lower lip was observed. Oral cavity can harbor a variety of manifestations related to renal transplantation under immunosuppressive therapy.

Epithelial-mesenchymal transition modulates lower lip carcinogenesis and promotes cancer progression.

OBJECTIVE: To investigate and compare the immunoexpression of E-cadherin, α-SMA, TGF-ß and Snail proteins between cases of actinic cheilitis (AC) and squamous cell carcinoma of the lower lip (LLSCC). STUDY DESIGN: E-cadherin, α-SMA, TGF-ß and Snail antibody immunostaining was analyzed semiquantitatively in 54 AC cases and in 49 LLSCCs. The cases were classified as low and high expression for analysis of the association with clinicopathological variables and overall survival (OS) and disease-free survival (DFS) rates. RESULTS: High expression of E-cadherin (cytoplasmic) (p = 0.001) and α-SMA (p < 0.001) was identified in LLSCCs, as well as low expression of TGF-ß in LLSCCs (p < 0.001) and high expression of Snail in AC cases (p = 0.006). Survival analysis revealed that high expression of α-SMA at the tumor invasion front, a network immunostaining pattern of this protein, and high expression of TGF-ß in tumor buds were significantly associated with poor OS (p < 0.05). There was a higher risk of death among LLSCC cases with high expression of α-SMA (HR = 5.90, p = 0.03). High expression of TGF-ß in tumor buds was significantly associated with poor DFS (p = 0.007) and with a higher risk of negative outcomes for DFS (HR = 4.44, p = 0.014). CONCLUSIONS: The present results suggest the potential involvement of dysregulation of proteins associated with epithelial-mesenchymal transition in the modulation of lip carcinogenesis and greater aggressiveness of LLSCC.