Relationship between aggressive features of oral squamous cell carcinoma and the immunoexpression of CX3CR1, CX3CL1 and ITGAV.

OBJECTIVE: We aimed to describe the association between CX3CR1, CX3CL1, and ITGAV immunoexpression with PNI and adverse oncologic outcomes in patients with OSCC. STUDY DESIGN: Expression CX3CR1, CX3CL1, and ITGAV was assessed by immunohistochemistry in a cohort of 50 paraffin-embedded resections of OSCC. Survival analysis, Cox, and binary logistic regressions were undertaken to determine the impact on patient survival and predictive value for PNI. RESULTS: CX3CL1 positive nerves exhibited a significant association with tumor budding (TB) (P = .043), whereas nerves positive for ITGAV were associated with PNI (P = .021), T3-T4 tumor size (P = .029), and III-IV stage (P = .044). Cases with ITGAV-positive nerves exhibited an odds ratio of 9.603 (P = .008) for PNI, whereas cases with CX3CL1-positive nerves exhibited and odds ratio of 4.682 (P = .033) for TB. A trend toward decreased 5-year overall survival (P = .078) and 5-year disease-specific survival (P = .09) was observed in relation to ITGAV-positive nerves. However, no independent predictors for poor survival were identified. CONCLUSIONS: The expression of ITGAV was associated with PNI and advanced disease, whereas the expression of CX3CL1 was related to TB, suggesting that ITGAV and CX3CL1 are involved in their respective developments. Therefore, further investigations are encouraged to assess the potential utility of targeted therapies against CX3CL1 receptors in OSCC.

CR5/CCL5 axis is linked to a poor outcome, and inhibition reduces metastasis in oral squamous cell carcinoma.

PURPOSE: The CCR5/CCL5 axis is essential for interactions between malignant cells and microenvironment components, promoting tumor progression in oral squamous cell carcinoma (OSCC). This study aims to evaluate the association of CCL5 and CCR5 with the behavior of oral cancer and assess the therapeutic potential of a CCR5 antagonist. METHODS: A retrospective study to analyze CCR5 and CCL5 expression on paraffin-embedded tissues was performed. In cell lines, rhCCL5 was added to induce CCR5-related pathways, and Maraviroc and shRNA against CCR5 were used to neutralize the receptor. Finally, an in vivo murine orthotopic xenograft model of tongue cancer was used to evaluate Maraviroc as an oncologic therapy. After 15 days, the mice were killed, and the primary tumors and cervical lymph nodes were analyzed. RESULTS: The expression of CCR5 was associated with clinical stage and metastasis, and CCL5 was related to overall survival. Adding rhCCL5 induced cell proliferation, while shRNA and Maraviroc reduced it in a dose-dependent manner. Maraviroc treatment also increased apoptosis and modified cytoskeletal organization. In vivo, Maraviroc reduced neck metastasis. CONCLUSIONS: The effects of CCR5 antagonists in OSCC have been poorly studied, and this study reports in vitro and in vivo evidence for the effects of Maraviroc in OSCC. Our results suggest that the CCR5/CCL5 axis plays a role in oral cancer behavior, and that its inhibition is a promising new therapy alternative.

Perineural invasion predicts poor survival and cervical lymph node metastasis in oral squamous cell carcinoma

Background: Oral squamous cell carcinoma (OSCC) usually invades peripheral nerves through a process known as perineural invasion (PNI), recognized as an adverse factor considered for the administration of postoperative adjuvant therapy. The aim of this study was to assess the impact of PNI on survival and cervical lymph node metastasis in a cohort of OSCC patients. Material and methods: Presence, location and extension of PNI were assessed in a cohort of 57 paraffin-embedded OSCC resections. Clinico-pathological variables were obtained from each case. Five-year overall survival (OS) and 5-year disease-specific survival (DSS) curves were constructed according to the Kaplan-Meier method and compared with log-rank test. The Cox proportional hazard model was used to assess the role of PNI as an independent risk factor related to poor survival, and a binary logistic regression was performed to estimate the predictive value of PNI for regional lymph node metastasis. Results: PNI was observed in 49.1% of the cases, affecting only small nerves. Peritumoral PNI was the most common location, and multifocal PNI the most frequent extent. Most PNI positive cases had cervical metastasis (p=0.001), and PNI was more frequent in stages III-IV than in I-II (p=0.02). The five-year OS and the 5-year DSS decreased in PNI positive and peritumoral PNI cases. PNI was an independent risk factor for poor 5-year OS and poor 5-year DSS. The odds for cervical lymph node metastasis were of 6.076 (p=0.006) and 10.257 (p=0.007) for PNI and Tumor budding (TB) positive cases, respectively. Conclusions: PNI is a frequent finding in OSCC and an independent risk factor for poor OS and DSS. PNI and TB are both risk factors associated to an increased likelihood for the development of lymph node metastasis. Therefore, we suggest further investigations to test the combined PNI-TB scoring system in risk stratification models for OSCC. (AU)

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

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[Pleomorphic adenoma on heterotopic salivary inclusion: case report and literature review]. / Adenoma pleomorfo sobre heterotopía salival: reporte de caso y revisión de la literatura.

Heterotopic salivary gland tissue is the presence of salivary tissue outside of the salivary glands. It is an uncommon condition but it can be the source of the full spectrum of salivary gland diseases. We present a rare case of pleomorphic adenoma developing from heterotopic salivary gland tissue in an upper neck lymph node not related to the major salivary glands. This article reviews the difficulty of the differential diagnosis with other cervical masses, embryogenesis, clinical manifestations and treatment of this condition.

La presencia de tejido salival fuera de las glándulas salivales se denomina heterotopía salival. Es poco frecuente, pero puede ser asiento de todo el espectro de patologías de las glándulas salivales. Se presenta un caso poco común de un adenoma pleomorfo en la región superior del cuello, desarrollado sobre una inclusión de tejido salival en un linfonodo, de manera independiente a las glándulas salivales. Se revisa la dificultad del diagnóstico diferencial dentro de las masas cervicales, su embriogénesis, manifestación clínica y tratamiento.

Historia natural del paciente alcohólico en la Comuna de Ancud / Natural history of the alcoholico patient in the Commune of Ancud

En el presente estudio se evaluó un grupo de 50 pacientes en control regular en el Hospital de Ancud por alcoholismo cuyo principal objetivo fue determinar la existencia de algún patrón evaluativo el cual tuviera valor estadístico, y la diferencia de acuerdo a la presencia de familiares alcohólicos de primer orden. Resultados: Si bien el grupo es pequeño para poder construir un gráfico predictivo, la tendencia mostró algún patrón evaluativo de la historia natural de esta enfermedad, con diferencia de acuerdo tengan o no los pacientes, familiares alcohólicos de primer grado; de esta manera creemos que este patrón puede ser estimado en estudios asociativos en otras comunidades para determinar la real relación biológica en esta enfermedad.