Analyses of VEGFC/VEGF-D expressions, density and endothelial lymphatic proliferation in salivary gland neoplasms.

OBJECTIVE: The aim of this study was to assess vascular endothelial growth factor C (VEGF-C) and VEGF-D expressions, tumor lymphatic density (D2-40) and endothelial lymphatic proliferation (D2-40/Ki-67 double labeling) in a series of salivary gland neoplasm cases. MATERIALS AND METHODS: Twenty pleomorphic adenomas (PA), 20 adenoid cystic carcinomas (ACC) and 20 mucoepidermoid carcinomas (MEC) were assessed, as well as 10 normal minor salivary gland (SG) tissues for comparison. RESULTS: All cases presented positive VEGF-C expression in the peritumoral and intratumoral regions, and no differences in immunoexpression were detected between groups. However, the ACC group presented a significant difference in VEGF-C immunoexpression according to the predominant histological pattern. Most cases presented poor VEGF-D labeling in the peritumoral and intratumoral regions. Concerning peritumoral, intratumoral and total lymphatic endothelial density, the assessed groups revealed an increasing gradient, with lower values for PA, followed by MEC and ACC. CONCLUSION: No correlation was detected between VEGF-C and VEGF-D immunoexpression in relation to lymphatic tumor density and endothelial lymphatic proliferation. Western blotting (WB) revealed no difference between VEGF-C and VEGF-D expression among the lesions, corroborating the immunohistochemistry findings.

Immunohistochemical analysis of myofibroblasts, TGF-ß1, and IFN-γ in epithelial odontogenic lesions.

AIM: To investigate the presence of myofibroblasts (MFBs) in epithelial odontogenic lesions by immunohistochemistry and to correlate the findings with tumor aggressiveness, as well as to analyze the expression of TGF-ß1 and IFN-γ during the differentiation of these cells. METHODS AND RESULTS: Twenty solid ameloblastomas (SAs), 10 unicystic ameloblastomas (UAs), 20 keratocystic odontogenic tumors (KCOTs), and 20 adenomatoid odontogenic tumors (AOTs) were selected. For evaluation of the presence of MFBs, anti-α-SMA-immunoreactive cells were quantified in connective tissue near the epithelium. The expression of TGF-ß1 and IFN-γ was evaluated in epithelial and connective tissue by determining the percentage of immunoreactive cells. A higher concentration of MFBs was observed in SAs (mean of 30.55), followed by KCOTs (22.50), UAs (20.80), and AOTs (19.15) (P = 0.001). There was no significant correlation between the immunoexpression of TGF-ß1 or IFN-γ and the number of MFBs (P > 0.05). CONCLUSIONS: The larger number of MFBs suggests that these cells are one of the factors responsible for the more aggressive biological behavior of these lesions. The lack of correlation between the number of MFBs and immunoexpression of TGF-ß1 and IFN-γ indicates that these proteins are not involved in the differentiation of this type of contractile cell in the lesions studied and that only the use of immunohistochemistry to establish such a correlation is a limiting factor.

Evaluation of the presence of Th1 response through T-bet and IFN-gamma immunohistochemical expression in lower lip and oral tongue squamous cell carcinomas.

INTRODUCTION: Evaluate the immunohistochemical expression of T-bet and IFN-γ in lower lip (LLSCC) and oral tongue squamous cell carcinoma (OTSCC), verifying the presence of Th1 responses in lesions with different clinical conditions. METHODS AND MATERIALS: Thirty OTSCC and 30 LLSCC were analyzed by immunohistochemistry. T-bet was quantitatively assessed by parenchyma cell and stroma quantification, and IFN-γ was semi-quantitatively analyzed: 1:0-25%; 2:26-50%; 3:51-75%; 4:> 75% immunopositive cells. Histological differentiation degrees were categorized as well differentiated (WD), moderately differentiated (MD), or poorly differentiated (PD). RESULTS: OTSCC presented the highest number of T-bet+, parenchyma (p: 0.006), stroma (p: 0.156), parenchyma/stroma (p: 0.015), with no relationship to histological malignancy grade. IFN-γ higher concentrations in LLSCC were detected in parenchyma, stroma and in parenchyma/stroma (p: 0.000), as well as greater immunoreactivity in WD and MD (p: 0.001). In OTSCC, a positive and statistically significant correlation was observed between T-bet+ in parenchyma and IFN-γ in stroma(r: 0.388; p: 0.034), in addition to a statistically significant positive correlation between T-bet in parenchyma compared to stroma(r: 0.411; p: 0.024) and for IFN-γ in both parenchyma and stroma(r: 0.775; p: 0.000) in LLSCC. Higher T-bet+ was observed in OTSCCs, although higher IFN-γ was detected in LLSCCs. CONCLUSION: Thus, we suggest that, even though LLSCC presented lower T-bet+, the favorable microenvironment in these lesions led to an expressive activation of IFN-γ by T-bet+, considerably acting on Th1 differentiation and in antitumor activity, which, admittedly, present less aggressive behavior, reinforcing once again the important role of this cytokine and its use in strategy to fight cancer.

BMP-2 and Noggin Immunoexpression in Ameloblastomas, Odontogenic Keratocysts, and Dentigerous Cysts.

BMP-2 and Noggin are expressed in several tissues and participate in cell differentiation and proliferation during odontogenesis and tumor development. We evaluated the immunohistochemical expression of these proteins in ameloblastomas (AMs), odontogenic keratocysts (OKCs), and dentigerous cysts (DCs). The expression in AM (n.20), OKC (n.20), and DC (n.20) was evaluated by the percentage of positive cells and expression intensity, resulting in a total immunostaining score. Analysis of BMP-2 and Noggin revealed positivity in all cases. The Mann-Whitney test showed a statistically significant difference for Noggin between AM and DC and between OKC/DC. The mean DC scores were always higher than those of the other groups, regardless of the assessment method. Individual analysis of each lesion showed a positive and significant correlation between the percentage of cells positive for BMP-2 and Noggin in DC. We demonstrated the presence of BMP-2 and Noggin in AMs/OKCs/DCs. Marked expression of BMP-2 was observed in OKCs and AMs. There was also a positive correlation between BMP-2 and Noggin in DCs, suggesting a greater role of these markers in the bone formation and remodeling process since DCs are characterized by phases of bone quiescence and healing.

Immunohistochemical study of the plasminogen activator system in benign epithelial odontogenic lesions.

The aim of this study was to analyze and compare the immunohistochemical expression of plasminogen activator system (PAS) proteins (uPA, uPAR, and PAI-1) in ameloblastomas (AMBs), odontogenic keratocysts (OKCs), and dental follicles (DFs) representing normal odontogenic tissue, as well as to investigate possible correlations between these proteins. Twenty AMBs, 20 OKCs, and 10 DFs were selected for immunohistochemical analysis. In each case, the immunoexpression of uPA, uPAR, and PAI-1 was evaluated semiquantitatively based on the percentage of positivity in odontogenic epithelial and connective tissue cells. The epithelial immunoexpression of uPA was significantly lower in AMBs when compared to OKCs (p = 0.001) and DFs (p = 0.029). Significantly higher epithelial immunostaining for uPAR was observed in AMBs when compared to OKCs (p < 0.001). There were no significant differences in the epithelial immunoexpression of PAI-1 between AMBs and OKCs (p = 1.000). The correlations found for the expression of the studied proteins were not statistically significant (p > 0.05). However, the epithelial and connective tissue expressions of uPAR have a strong positive and statistically significant correlation in AMBs. The present results suggest that uPA is involved in the pathogenesis of OKCs and that uPAR may participate in tumorigenesis in AMBs. The high percentage of PAI-1-positive cells suggests a possible role for this protein in the development of AMBs and OKCs. Furthermore, the studied proteins do not seem to act synergistically in AMBs, OKCs, and DFs.

ALDH1 expression and potential clinical implications in chronic inflammatory periapical lesions.

Aldehyde dehydrogenase 1 (ALDH-1) is a marker of stem cells in a variety of diseases, but its role in individuals with chronic inflammatory periapical lesions remains unknown. The aim of this study was to investigate the presence of cells with a stem cell profile based on the immunoexpression of ALDH-1 in periapical granulomas (PGs) and radicular cysts (RCs). A total of 51 cases of periapical lesions (25 PGs and 26 RCs) were subjected to immunohistochemical study. The anti-ALDH-1 antibody was applied using the immunoperoxidase technique. An immunoexpression score (intensity vs. percentage of cells) was used, with the cases being classified as low expression (score: 0 to 4) and high expression (score: 6 to 9). The Chi-square test was used with a 5% level of significance. Immunoexpression of ALDH-1 was detected in all cases of PGs and RCs. In PG cases, the expression was diffuse in connective tissue cells, with most cases exhibiting high expression (n = 18; 69.2%), while in RC cases the expression revealed focal distribution in cells of the capsule and epithelial cells of the cystic lining, with most cases classified as low expression (n = 18; 72%). Significant differences in the expression scores of ALDH-1 were observed in PGs (p = 0.003). The variable expression of ALDH-1 suggests the presence of cells with stem cell profiles in PGs and RCs. These findings suggest that periapical tissues infiltrated by chronic inflammation can recruit important cells for the repair or evolution of periapical lesions.

Botryoid odontogenic cyst: a clinicopathologic study of 10 cases.

Botryoid odontogenic cyst is a rare multilocular variant of lateral periodontal cysts. In this study, a series of 10 cases of botryoid odontogenic cysts retrieved from the archives of the Postgraduation Program in Oral Pathology, Federal University of Rio Grande do Norte (Brazil), were reviewed for epidemiologic data, clinical presentation, radiographic and histopathologic characteristics, treatment, and recurrence.

Immunohistochemical expression of OCT4 and CD44 in major and minor salivary gland neoplasms.

The aim of this study was to identify tumor parenchyma cells exhibiting immunohistochemical profile of stem cells by evaluating the immunoreactivity of OCT4 and CD44 in a number of cases of salivary gland neoplasms. The sample consisted of 20 pleomorphic adenomas, 20 mucoepidermoid carcinomas, and 20 adenoid cystic carcinomas located in major and minor salivary glands. The expression of OCT4 and CD44 was evaluated by the percentage of positive cells and the intensity of expression. All studied cases showed positive expression of OCT4 and CD44 and higher values than the control groups. For OCT4, luminal and non-luminal cells were immunostained in the case of pleomorphic adenomas and adenoid cystic carcinomas. Moreover, the immunoreactivity of CD44 was particularly evident in the non-luminal cells of these lesions. In mucoepidermoid carcinomas, there was immunoreactivity for both markers in squamous and intermediate cells and absence of staining in mucous cells. For both markers, a significantly higher immunostaining was verified in neoplasms located in the major salivary glands compared with lesions in minor salivary glands (p<0.001). In the total sample and in minor salivary glands, malignant neoplasms exhibited higher immunoreactivity for OCT4 than pleomorphic adenoma. A significant moderate positive correlation (r = 0.444 and p ≤ 0.001) was found between OCT4 and CD44 immunoexpression in the total sample. The high expression of OCT4 and CD44 may indicate that these proteins play an important role in identifying tumor stem cells.

Role of Twist and Podoplanin in Partial Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma.

The aim of this study was to perform a comparative analysis of podoplanin (PDPN) and Twist immunoexpressions in lower lip and oral tongue squamous cell carcinomas (LLSCC and OTSCC, respectively). PDPN and Twist immunoexpressions were semi-quantitatively evaluated by analyzing the invasion front, the compressive areas, the large islands and nests and dissociated cells of the chosen carcinomas. Their statistical associations and correlations with clinical-pathological characteristics were verified by the Mann-Whitney and Spearman's test. Twist expression was low in both carcinomas, with <25% labeling on the invasive front. Significant differences were observed for LLSCC (p=0.032) and OTSCC (p=0.025) regarding PDPN immunoexpression in relation to the worst invasion patterns determined by a histological malignancy gradation system. Statistically significant negative correlations between PDPN membrane expression and general (r=-0.356, p=0.024) and cytoplasmic Twist expressions (r=-0.336; p=0.034) in LLSCC were also observed. Twist and PDPN are suggested to be associated to a more aggressive invasion pattern in both LLSCC and OTSCC cases but not related to the different biological behaviors on these anatomical sites. Also, it was seen that PDPN membrane expression is inversely related to general and cytoplasmic Twist expression in LLSCC cases.

Caliber Persistent Artery in the Upper Lip: A Case Report with Unusual Histopathological Findings.

Caliber persistent labial artery (CPLA) consists in a dilated portion of the main branch of the labial artery without loss of size. The aim of this study is to report a case of a patient diagnosed with CPLA in the upper lip, emphasizing unusual histopathological and immunohistochemical findings. A 67-year-old female patient with complaint of a pulsating upper lip lesion without painful symptomatology. Under a clinical diagnosis of CPLA, and considering that the patient was edentulous and used a total prosthesis, an excisional biopsy of the lesion was performed to avoid future traumas in the region and consequently possible exuberant local bleeding. At anatomopathological examination structures suggestive of lymphoid follicles and germinal centers were visualized. Immunohistochemistry showed positivity for CD20, CD68, desmin and CD34 and negativity for CD4. The patient did not have a history of allergies, cardiovascular, rheumatic or systemic diseases that could justified the findings. The case presents unusual histopathological structures, evidencing the necessity of more studies about this pathology so scarce in the literature.

Polymorphisms of matrix metalloproteinase-7 and -9 are associated with oral tongue squamous cell carcinoma.

Matrix degradation is an important event in the progression, invasion and metastasis of malignant head and neck lesions. Imbalances, mutations and polymorphisms of MMPs and their inhibitors are observed in several cancer subtypes. The aim of this study was to evaluate the association of the MMP-7 gene promoter (181 A/G) and MMP-9 (-1562 C/T) polymorphisms in oral tongue squamous cell carcinoma (OTSCC). MMP-7 (rs11568818) and MMP-9 (rs3918242) single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 71 cases of OTSCC. Normal tissue specimens were obtained from 60 healthy volunteers to serve as the control. The MMP-7 G allele and MMP-9 T allele were more frequent in the OTSCC group than the control group, but only when these two SNPs were taken together was a significant association found with the nodal metastasis of OTSCC (p < 0.001). Based on our results, SNPs in the promoter region of MMP-7 and MMP-9 appear to be associated with greater risk of developing OTSCC, and with a higher propensity to form metastatic tumors. In this respect, molecular studies investigating polymorphisms may be useful in predicting tumor behavior.

Immunoexpression of DNA base excision repair and nucleotide excision repair proteins in ameloblastomas, syndromic and non-syndromic odontogenic keratocysts and dentigerous cysts.

OBJECTIVE: To evaluate the immunoexpression of DNA base excision repair (BER) [apurinic/apyrimidinic endonuclease 1 (APE-1), X-ray repair cross complementing 1 (XRCC-1)] and nucleotide excision repair (NER) [xeroderma pigmentosum complementation group (XPF)] proteins in benign epithelial odontogenic lesions with different biological behaviors. DESIGN: Thirty solid ameloblastomas, 30 non-syndromic odontogenic keratocysts (NSOKCs), 29 syndromic odontogenic keratocysts (SKOCs), 30 dentigerous cysts (DCs) and 20 dental follicles (DFs) were evaluated quantitatively for APE-1, XRCC-1 and XPF through immunohistochemistry. RESULTS: Nuclear expression of APE-1 was significantly higher in NSOKCs, SOKCs, and ameloblastomas in comparison to DCs (p < 0.001). Nuclear expression of XRCC-1 was higher in NSOKCs and SOKCs than in DCs (p < 0.05). At the nuclear level, XPF expression was higher in NSOKCs and SOKCs than in DCs and ameloblastomas (p < 0.05). A statistically significant higher expression of APE-1 (nuclear), XRCC-1 (nuclear), and XPF (nuclear and cytoplasmic) was found in all odontogenic lesion samples as compared to DFs (p < 0.05). For all lesions, there was a positive correlation between nuclear expression of APE-1 and XRCC-1 or XPF (p < 0.05). CONCLUSIONS: Our results suggest a potential involvement of APE-1, XRCC-1 and XPF proteins in the pathogenesis of benign epithelial odontogenic lesions, especially in those with more aggressive biological behavior, such as ameloblastomas, NSOKCs, and SOKCs. We also showed that the expression of APE-1 was positively correlated with the nuclear expression of XRCC-1 and XPF, which may suggest an interaction between the BER and NER pathways in all odontogenic lesions studied herein.

Immunohistochemical evaluation of HLA-G and FoxP3+ T regulatory cells in oral cavity and lower lip squamous cell carcinomas.

Human Leukocyte Antigen G (HLA-G) is a molecule involved in the tumor immunosuppression and also in the generation of regulatory T (Treg) cells, thus leading to evasion to the immune system host, and consequently, contributing to tumor progression in several cancers. The aim of this study was to evaluate the immunoexpression of HLA-G by tumor cells and FoxP3+ Treg cells in 25 oral tongue squamous cell carcinomas (SCCs) and 25 lower lip SCCs and analyze their relationship with clinical parameters. HLA-G expression was higher in oral tongue SCCs than in lower lip SCCs. In oral tongue SCCs and lower lip SCCs, no association between HLA-G expression and clinical parameters (tumor size, lymph node status, distant metastasis, and clinical stage) was verified (P>0.05). FoxP3+ Treg cells were detected along the tumor invasive front in all cases of oral tongue and lower lip SCCs. In oral tongue SCC cases, the number of Treg cells tended to be higher in smaller tumors, tumors without regional lymph node metastasis, and tumors in early clinical stages, but the difference was not statistically significant (P>0.05). A significant positive correlation was found between the expression of HLA-G by neoplastic cells and Treg cells in lower lip SCCs (p = 0.008). Our findings suggest the involvement of HLA-G and Treg cells in the modulation of immune responses in oral tongue and lower lip SCCs. This interaction between HLA-G and Treg cells may represent an evasion mechanism in these malignancies.

Malignant salivary gland tumors: agreement between fine needle aspiration biopsy, incisional biopsy and final histopathological diagnostic / Tumores malignos de glándulas salivales: concordancia entre biopsia por aspiración con aguja fina, biopsia incisional y diagnóstico histopatológico final

Background: Incisional biopsy is indicated for intraoral tumors, but it is a contraindicated surgical procedure formajor salivary glands. To avoid complications and facilitate diagnosis, fine needle aspiration biopsy (FNAB) is atype of biopsy widely used for preoperative diagnosis in these glands.Material and Methods: The aim of this study was to analyze the agreement between the diagnosis by FNAB (ma-jor glands), incisional biopsy (minor glands) and histopathological analysis of the surgical specimen in salivarygland tumors from a database (medical records) of patients treated in a cancer treatment reference center in theNortheast region of Brazil.Results: The sample consisted of 110 cases, being 86 of them malignant tumors in major salivary glands (parotidgland=73; submandibular gland=13) and 24 cases in minor salivary glands (palate). The female gender was themost affected (57.3%), especially in patients over 60 years (42.7%). In the TNM classification, 41.8% of the caseswere in T2 at the time of diagnosis, with most of the regional lymph nodes in N0 (85.5%) and 87.3% of the casesin M0. FNAB was able to identify malignant neoplasms in 68.6% of the cases (n=59), while incisional biopsy inpalatal tumors obtained agreement of 75% of the cases (n=18). The analysis revealed that tumors classified as T3-T4 (p=0.012) showed greater agreement between pre- and post-surgical diagnosis.(AU)

Expression of urokinase-type plasminogen activator and its receptor in squamous cell carcinoma of the oral tongue.

Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) act in the proteolysis of basement membrane and extracellular matrix structures, facilitating tumor invasion. The purpose of this study was to evaluate the relationship between these proteins and clinicopathological parameters in squamous cell carcinoma of the oral tongue (SCCOT). Sixty cases of SCCOT were submitted to immunohistochemistry and analyzed semiquantitatively at the invasion front and in the tumor core. The results were associated with lymph node metastasis, clinical stage, locoregional recurrence, clinical outcome and histological grade of malignancy. A higher expression of uPA was observed in cases of tumors of high-grade versus low-grade malignancy (p = 0.010). Moreover, the cases with the worst pattern of invasion presented an overexpression of uPA (p = 0.011). The presence of locoregional recurrence was associated with uPAR (p = 0.039), and the expression of both biomarkers was much higher at the invasion front than in the tumor core (p < 0.001). The results suggest uPA and uPAR are involved in the progression and aggressiveness of SCCOT, mainly at the tumor-host interface.

Participation of hypoxia-inducible factor-1α and lymphangiogenesis in metastatic and non-metastatic lower lip squamous cell carcinoma.

This study evaluated the lymphatic density and HIF-1α immunoexpression in lower lip squamous cell carcinoma (LLSCC) and their correlation with clinicopathological (nodal metastasis, clinical stage, histological grade, recurrence and disease outcome) and survival parameters in 20 metastatic and 20 non-metastatic LLSCCs. Lymphatic density was established by counting microvessels (D2-40+) at the tumor core (intratumoral lymphatic density, ILD) and at the invasive front (peritumoral lymphatic density, PLD) and percentages of immunopositive cells for HIF-1α were established. No statistically significant differences in lymphatic densities in relation to clinicopathological parameters were observed (P > 0.05). All cases exhibited nuclear and cytoplasmic HIF-1α immunoexpression, with relatively high percentages of positivity, but this expression was not statistically different in relation to clinicopathological variables (P > 0.05). Positive correlations were observed between ILD and PLD (P = 0.002), and between nuclear HIF-1α immunoexpression at the tumor core and ILD (P = 0.001). The results suggest ILD and PLD are not directly related to the development of lymph node metastasis in LLSCC. The striking expression of HIF-1α suggests the involvement of this protein in the etiopathogenesis of LLSCCs, possibly stimulating lymphangiogenesis at the tumor core. However, this protein does not seem to exert a determining influence on the biological aggressiveness of these tumors.

Immunohistochemical expression of myofibroblasts, TGF-ß1 and IFN-γ in oral fibrous lesions.

OBJECTIVE: Analyze the presence of myofibroblasts (MFBs) in oral fibrous lesions and investigate TGF-ß1 and IFN-γ expression by immunohistochemistry during their differentiation. DESIGN: Twenty giant cell fibromas (GCFs), 20 fibromas (FIBs), and 20 fibrous hyperplasias (FHs) were selected. To evaluate the presence of MFBs, anti-α-SMA-immunoreactive cells were quantified in connective tissue. TGF-ß1 and IFN-γ expressions were evaluated in epithelial and connective tissue by determining the percentage of immunoreactive cells. RESULTS: Higher MFBs concentrations were observed in GCFs (median of 20.00), followed by FHs (15.00) and FIBs (14.00) (P = 0.072). No significant correlation between TGF-ß1 or IFN-γ immunoexpression and the number of MFBs in oral fibrous lesions was observed (P > 0.05). CONCLUSIONS: The higher density of MFBs found in GCFs, followed by FHs and FIBs, reaffirms the fibrogenic role of these cells, while the higher concentrations detected in GCFs, including evidence of giant MFBs, also suggest a role in the neoplastic behavior of these lesions. No correlation was observed between TGF-ß1 and IFN-γ in the myofibroblastic transdifferentiation process of the analyzed lesions.

Immunohistochemical analysis of lymphatic vessel density and mast cells in oral tongue squamous cell carcinoma.

The aim of this study was to analyze lymphangiogenesis and the presence of mast cells in oral tongue squamous cell carcinoma (OTSCC), correlating the findings with clinicopathological parameters (clinical stage, tumor size, nodal metastasis, histological grade of malignancy, local recurrence, and clinical outcome). Fifty-six cases of primary OTSCC were selected. Lymphatic vessels and mast cells were identified by immunostaining with anti-podoplanin (D2-40) and anti-tryptase antibody, respectively. Lymphatic vessel density (LVD) and mast cell density (MCD) were determined in the intratumoral and peritumoral areas. Intratumoral LVD was higher in advanced clinical stages (III/IV) when compared to early-stage (p = 0.017) and in metastatic cases compared to non-metastatic tumors (p = 0.013). Peritumoral LVD and intratumoral or peritumoral MCD did not differ significantly according to the clinicopathological parameters of OTSCCs (p > 0.05). No significant correlations between LVD and MCD were observed at the intratumoral (r = -0.014; p = 0.918) or peritumoral level (r = 0.156; p = 0.251). Our findings suggest that intratumoral lymphatic vessels, compared to peritumoral lymphatic vessels, appear to be more related to the progression of OTSCC. MCD alone does not seem to be determinant for lymphangiogenesis or for the biological behavior of OTSCC, indicating multiple pro- and antitumor effects of these inflammatory cells.

Immunoexpression of BMP-2 and BMP-4 and their receptors, BMPR-IA and BMPR-II, in ameloblastomas and adenomatoid odontogenic tumors.

OBJECTIVES: The present study evaluated the immunohistochemical expression of BMP-2 and BMP-4 and of their receptors (BMPR-IA and BMPR-II) in solid ameloblastoma (SA), unicystic ameloblastoma (UA) and adenomatoid odontogenic tumor (AOT) in order to obtain a better understanding of their role in the development and biological behavior of these tumors. DESIGN: This study analyzed these proteins in 30 cases of SA, 10 cases of UA, and 30 cases of AOT. Immunoexpression was evaluated in the parenchyma and stroma by attributing the following scores: 0, no stained cells; 1, ≤10%; 2, >10% and ≤25%; 3, >25% and ≤50%; 4, >50% and ≤75%.; 5, >75% stained cells. RESULTS: In SAs, positive correlations were observed between the stromal and parenchymal expression of BMP-2 (p<0.001) and between the stromal expression of BMP-2 and BMP-4 (p=0.020), as well as between the stromal expression of BMPR-II and BMP-4 (p=0.001) and the stromal and parenchymal expression of BMPR-II (p<0.001). In UAs, correlations were detected between the stromal and parenchymal expression of BMP-4 (p=0.035) and between the stromal expression of BMP-4 and BMPR-IA (p=0.022). In AOTs, analysis of immunoexpression in the parenchyma revealed positive correlations between all proteins. CONCLUSION: BMPs and their receptors play an important role in the differentiation and development of ameloblastomas and AOTs, but may not explain the different biological behaviors of these lesions. The positive correlation observed in AOTs might be related to the formation of mineralized material in this tumor.

Analysis of GLUT-1, GLUT-3, and angiogenic index in syndromic and non-syndromic keratocystic odontogenic tumors.

The aim of this study was to evaluate the immunoexpression of glucose transporters 1 (GLUT-1) and 3 (GLUT-3) in keratocystic odontogenic tumors associated with Gorlin syndrome (SKOTs) and non-syndromic keratocystic odontogenic tumors (NSKOTs), and to establish correlations with the angiogenic index. Seventeen primary NSKOTs, seven recurrent NSKOTs, and 17 SKOTs were selected for the study. The percentage of immunopositive cells for GLUT-1 and GLUT-3 in the epithelial component of the tumors was assessed. The angiogenic index was determined by microvessel count. The results were analyzed statistically using the nonparametric Kruskal-Wallis test and Spearman's correlation test. High epithelial immunoexpression of GLUT-1 was observed in most tumors (p = 0.360). There was a higher frequency of negative cases for GLUT-3 in all groups. The few GLUT-3-positive tumors exhibited low expression of this protein in epithelial cells. No significant difference in the angiogenic index was observed between groups (p = 0.778). GLUT-1 expression did not correlate significantly with the angiogenic index (p > 0.05). The results suggest that the more aggressive biological behavior of SKOTs when compared to NSKOTs may not be related to GLUT-1 or GLUT-3 expression. GLUT-1 may play an important role in glucose uptake by epithelial cells of KOTs and this process is unlikely related to the angiogenic index. GLUT-1 could be a potential target for future development of therapeutic strategies for KOTs.