Involvement of tryptase-positive mast cells and angiogenesis in the growth of inflammatory odontogenic cysts

Abstract: Inflammatory periapical lesions are characterized by infiltration of different immune cell types, the functions of which depend on an effective vascular network. This study aimed to evaluate the mast cells density (MCD) in inflamatory odontogenic cysts capsules concerning microvascular density (MVD), microvascular area (MVA), and microvascular perimeter (MVP), and correlate such findings with the type of lesion, intensity of the inflammatory infiltrate, and thickness of the epithelial lining. Twenty inflamatory dentigerous cysts (IDCs), twenty radicular cysts (RCs), and twenty residual radicular cysts (RRCs) were submitted to immunohistochemical analysis using anti-tryptase and anti-CD34 antibodies. RCs exhibited the highest MCD, MVD, MVA, and MVP indexes (p = < 0.001, p = 0.008, p = 0.003 and p = < 0.001, respectively), and lesions with inflammatory infiltrate grade III showed the highest MVD (p = 0.044). Considering epithelial thickness, a higher MVP index was identified in lesions with hyperplastic epithelium (p = 0.018). In IDCs, RCs, and RRCs, a strong positive correlation was observed between MVA and MVP (r = 0.950 and p = < 0.001; r = 0.914 and p = < 0.001; r = 0.713 and p = < 0.001, respectively). In IDCs, a moderate correlation was observed between MCD and both MVA and MVP (r = 0.660 and p = 0.002; r = 0.634 and p = 0.003, respectively). These results suggest that tryptase-positive mast cells might play an important role in the angiogenic activity of IDCs, while RCs had the highest indexes. Our findings also confirmed that the intensity of the inflammatory infiltrate and epithelial thickness influence angiogenesis.

Macrophages subpopulations in chronic periapical lesions according to clinical and morphological aspects

Abstract: The aim of this study was to evaluate macrophage M1 and M2 subpopulations in radicular cysts (RCs) and periapical granulomas (PGs) and relate them to clinical and morphological aspects. M1 macrophages were evaluated by the percentage of CD68 immunostaining associated with the inflammatory cytokine TNF-α, and M2 macrophages, by its specific CD163 antibody. The CD68+/CD163+ ratio was adopted to distinguish between the two macrophage subpopulations. Clinical, radiographic, symptomatology, treatment, and morphological parameters of lesions were collected and a significance level of p = 0.05 was adopted for statistical analysis. The results showed that the CD68+/CD163+ ratio was higher in the RCs (median = 1.22, p = 0.002), and the highest TNF-α immunostaining scores were found in RCs (p = 0.018); in PGs, the CD68+/CD163+ ratio was lower and associated with a greater CD163+ immunostaining (median = 1.02, p <0.001). The TNF-α in cyst epithelium had a score of 3 in 10 cases and predominance of M1 macrophages by CD68+/CD163+ (median = 2.23). In addition, CD68+ cells had higher percentage of immunostaining in smaller RCs (p = 0.034). Our findings suggest that increased CD68 immunostaining associated with TNF-α cytokine in RCs results in a greater differentiation of the M1 phenotype. The higher CD163 immunostaining in PGs results in greater differentiation of the M2 phenotype. Therefore, the inflammatory state promoted by M1 macrophages is related to growth and progression of RCs; on the other hand, the immunomodulatory state of M2 macrophages is related to maintenance of PGs.

Estaniocalcina 2 modula eventos importantes para a tumorigênese oral e é um marcador prognóstico para pacientes com carcinoma de células escamosas oral / Staniocalcin 2 modulates important events for oral tumorigenesis and is a prognostic marker for patients with oral squamous cell carcinoma

O hormônio glicoproteico estaniocalcina 2 (STC2) está envolvido na carcinogênese e progressão de muitos tipos de câncer. No entanto, seu significado clínico e mecanismos moleculares no carcinoma de células escamosas oral (CCEO) foram pouco estudados e permanecem incertos. O presente estudo investigou associações da expressão da STC2 com parâmetros clinicopatológicos e de sobrevida em pacientes com CCEO. Além disso, foram avaliados os efeitos biológicos causados pela redução dos níveis de STC2 em linhagens celulares de CCEO e fibroblastos associados ao câncer (do inglês CAF ­ carcinoma associated fibroblasts). A análise imunoistoquímica em 100 casos de CCEOs primários indicou que a superexpressão da STC2 foi associada com o parâmetro N do sistema TNM e foi um fator de risco independente para sobrevida específica da doença e sobrevida livre de doença em pacientes com CCEO. Usando ensaios in vitro, foi demonstrado que o silenciamento da STC2 em linhagens de CCEO promoveu a apoptose e reduziu a proliferação celular, migração, invasão e transição epitélio-mesenquimal. Análises adicionais revelaram que o CAF expressa maiores níveis de STC2 do que as células de CCEO. O silenciamento da STC2 no CAF reduziu a invasão celular do CCEO, sugerindo que a STC2 liberada por CAFs contribui para um fenótipo mais invasivo no CCEO. Esses resultados sugerem que a STC2 modula eventos importantes para a tumorigênese oral e pode ser um biomarcador prognóstico para pacientes com CCEO (AU).

The glycoprotein hormone stanniocalcin 2 (STC2) is involved in carcinogenesis and progression of several cancer types. However, its clinical significance and molecular mechanisms in oral squamous cell carcinoma (OSCC) have been partially studied and remain uncertain. In the present study, we investigated associations of STC2 expression with clinicopathological and survival parameters of OSCCs patients. We also determined the biological effects caused by STC2 downregulation in OSCC and cancer associated fibroblasts (CAF) cell lines. Immunohistochemical analysis in 100 cases of primary OSCC indicated that STC2 overexpression was associated with N stage (TNM staging) and was an independent risk factor for disease-specific survival and disease-free survival in patients with OSCC. Using in vitro assays, we demonstrated that STC2 knockdown in OSCC cell lines promoted apoptosis, and reduced cell proliferation, migration, invasion and epithelial-mesenchymal transition. Further analysis revealed that CAF expresses higher levels of STC2 than OSCC cells. Knockdown of STC2 in CAF reduced OSCC cell invasion, suggesting that STC2 released by CAF contributes to a more invasive phenotype in OSCC. These results suggest that STC2 modulates important events for oral tumorigenesis and can be a prognostic biomarker for OSCC (AU).