Oral Mucosal Melanoma: A Case Report and Literature Review

ABSTRACT: Oral mucosal melanoma is an unusual and aggressive malignant tumor that mainly affects the palate of men aged between 50 and 60 years. We present a literature review focusing on the etiopathogenesis and the clinicopathologic features of this entity. In addition, we reported a rare case of an oral mucosal melanoma arising in the left cheek of a 60-yea r- old man. Computed tomography scan revealed infiltration of the tumor to other anatomic structures including the maxillary sinus, the zygomatic bone and the pterygoid processes. Based on its extension, the lesion was considered inoperable and treatment with three-dimensional conformal radiation therapy was proposed but the patient only attended to the first session and died from cancer progression 6 months after the diagnosis. This paper reinforces the importance of inclusion of this malignant tumor in the differential diagnosis of pigmented lesions of the oral mucosa.

RESUMEN: El melanoma de la mucosa oral es un tumor maligno inusual y agresivo que afecta principalmente al paladar de hombres de entre 50 y 60 años. Presentamos una revisión bibliográfica centrada en la etiopatogenia y las características clínico-patológicas de esta entidad. Además, reportamos un caso raro de melanoma de la mucosa oral que surgió en la mejilla izquierda de un hombre de 60 años. La tomografía computarizada reveló la infiltración del tumor a otras estructuras anatómicas, incluido el seno maxilar, el hueso cigomático y los procesos pterigoideos. En base a su extensión, la lesión se consideró inoperable y se propuso tratamiento con radioterapia conformada tridimensional pero el paciente solo asistió a la primera sesión y falleció por progresión del cáncer 6 meses después del diagnóstico. Este trabajo refuerza la importancia de la inclusión de este tumor maligno en el diagnóstico diferencial de las lesiones pigmentadas de la mucosa oral.

Correlation of Beta-2 Adrenergic Receptor Expression inTumor-Free Surgical Margin and at the Invasive Front ofOral Squamous Cell Carcinoma

Background. The beta-2 adrenergic receptor is expressed by neoplastic cells and is correlated with a wide spectrum of tumor cell mechanisms including proliferation, apoptosis, angiogenesis, migration, and metastasis. Objectives. The present study aimed to analyze the expression of the beta-2 adrenergic receptor (ß2-AR) in tumor-free surgical margins of oral squamous cell carcinomas (OSCC) and at the invasive front. Sixty-two patients diagnosed with OSCC, confirmed by biopsy, were selected for the study. The clinicopathological data and clinical follow-up were obtained from medical records and their association with ß2-AR expression was verified by the chi-square test or Fischer's exact test. To verify the correlation of ß2-AR expression in tumor-free surgical margins and at the invasive front of OSCCs, Pearson's correlation coefficient test was applied. Results. The expression of ß2-AR presented a statistically significant correlation between the tumor-free surgical margins and the invasive front of OSCC (r = 0.383; p = 0.002). The immunohistochemical distribution of ß2-AR at the invasive front of OSCC was also statistically significant associated with alcohol (p = 0.038), simultaneous alcohol and tobacco consumption (p = 0.010), and T stage (p = 0.014). Conclusions. The correlation of ß2-AR expression in OSCC and tumor-free surgical margins suggests a role of this receptor in tumor progression and its expression in normal oral epithelium seems to be constitutive

Migração e invasão do câncer de boca via ativação de receptor beta 2 adrenérgico por mediador do estresse / Cell migration and invasion of oral cancer via activation of beta 2 adrenergic receptor by stress mediator

A ativação do receptor beta 2 adrenérgico (β2-AR), pelos mediadores químicos do estresse, pode induzir efeitos estimuladores ou inibidores na migração e invasão celular, dependendo do tipo de tumor maligno. A importância deste receptor na evolução do câncer de boca não está totalmente esclarecida. O objetivo deste estudo foi verificar a expressão do β2-AR em linhagens de carcinomas espinocelular de boca (SCC-9 e SCC-25), e investigar o papel da ativação deste receptor pela norepinefrina e de seu bloqueio por um antagonista na migração e invasão destas células neoplásicas. As células SCC-9 e SCC-25 foram investigadas quanto à expressão gênica e proteica do β2-AR, respectivamente, pelo RT-qPCR e pelo Western blot. A migração e a invasão celular foram analisadas pelo ensaio de cicatrização de feridas e pelo sistema de câmeras de invasão Transwell, respectivamente. Diferentes concentrações (0,1; 1 e 10μM) de norepinefrina foram utilizadas para estimular e 1μM de propranolol foi empregado para bloquear os receptores beta adrenérgicos nas células neoplásicas. As diferenças das médias obtidas nos experimentos de invasão e migração de SCC-9 e SCC-25 e da expressão proteica do β2-AR, foram comparadas pelo teste t de Student com nível de significância de 5%. Os resultados mostraram que a expressão gênica e proteica do β2-AR foi verificada em ambas as linhagens de câncer de boca. A concentração de 10μM de norepinefrina inibiu, significativamente (p≤0,05), a migração e invasão celular de SCC-9 e SCC-25, sendo este efeito mais acentuado nas células SCC-25. Além disso, houve uma redução significativa (p≤0,05) do efeito da norepinefrina na migração celular quando os β2-AR foram inibidos pelo propranolol. Adicionalmente, o bloqueio dos β-ARs pelo propranolol reverteu parcialmente o efeito da norepinefrina na capacidade invasiva de SCC-9 e SCC-25. Estes resultados comprovam que a norepinefrina, via ativação do β2-AR, reduziu a migração e a invasão das...

The activation of beta 2 adrenergic receptor (β2-AR), by chemical mediators of stress, can induce stimulatory or inhibitory effects on cell migration and invasion, depending on the type of malignancy. The importance of this receptor in the oral cancer outcome is not fully understood. The aim of this study was to verify β2- AR expression in oral squamous cell carcinoma cell lines (SCC-9 and SCC-25), and to investigate the role of activation of this receptor by norepinephrine and its blockade by an antagonist in migration and invasion of these neoplastic cells. SCC-9 and SCC-25 cells were investigated for gene and protein expression of β2-AR, respectively, by RT-qPCR and Western blot. The cell migration and invasion were analyzed by wound healing assay and Transwell invasion camera system, respectively. Different concentrations (0.1, 1 and 10μM) of norepinephrine were used to stimulate and 1μM propranolol was used to block the beta adrenergic receptors on cancer cells. Differences in mean values of the invasion and migration assays of SCC-9 and SCC-25 and β2-AR protein expression were compared by the Student t test with 5% significance level. The results showed that β2-AR gene and protein expression was verified in both oral cancer cell lines. The concentration of 10μM of norepinephrine inhibited significantly (p≤0.05), cell migration and invasion of SCC-9 and SCC-25, being the most pronounced effect in SCC-25 cells. Furthermore, there was a significant reduction (p≤0.05) of norepinephrine effect on cell migration when the β2-AR was inhibited by propranolol. In addition, blockade of β-ARs by propranolol partially reversed the effect of norepinephrine on the invasiveness of SCC-9 and SCC-25. These results show that norepinephrine via β2-AR activation, reduced the migration and invasion of oral squamous cell carcinoma cells and, therefore, the use of beta-adrenergic receptors agonists could become an adjuvant therapeutic target in the treatment of this malignancy...

Migração e invasão do câncer de boca via ativação de receptor beta 2 adrenérgico por mediador do estresse / Cell migration and invasion of oral cancer via activation of beta 2 adrenergic receptor by stress mediator

A ativação do receptor beta 2 adrenérgico (β2-AR), pelos mediadores químicos do estresse, pode induzir efeitos estimuladores ou inibidores na migração e invasão celular, dependendo do tipo de tumor maligno. A importância deste receptor na evolução do câncer de boca não está totalmente esclarecida. O objetivo deste estudo foi verificar a expressão do β2-AR em linhagens de carcinomas espinocelular de boca (SCC-9 e SCC-25), e investigar o papel da ativação deste receptor pela norepinefrina e de seu bloqueio por um antagonista na migração e invasão destas células neoplásicas. As células SCC-9 e SCC-25 foram investigadas quanto à expressão gênica e proteica do β2-AR, respectivamente, pelo RT-qPCR e pelo Western blot. A migração e a invasão celular foram analisadas pelo ensaio de cicatrização de feridas e pelo sistema de câmeras de invasão Transwell, respectivamente. Diferentes concentrações (0,1; 1 e 10μM) de norepinefrina foram utilizadas para estimular e 1μM de propranolol foi empregado para bloquear os receptores beta adrenérgicos nas células neoplásicas. As diferenças das médias obtidas nos experimentos de invasão e migração de SCC-9 e SCC-25 e da expressão proteica do β2-AR, foram comparadas pelo teste t de Student com nível de significância de 5%. Os resultados mostraram que a expressão gênica e proteica do β2-AR foi verificada em ambas as linhagens de câncer de boca. A concentração de 10μM de norepinefrina inibiu, significativamente (p≤0,05), a migração e invasão celular de SCC-9 e SCC-25, sendo este efeito mais acentuado nas células SCC-25. Além disso, houve uma redução significativa (p≤0,05) do efeito da norepinefrina na migração celular quando os β2-AR foram inibidos pelo propranolol. Adicionalmente, o bloqueio dos β-ARs pelo propranolol reverteu parcialmente o efeito da norepinefrina na capacidade invasiva de SCC-9 e SCC-25. Estes resultados comprovam que a norepinefrina, via ativação do β2-AR, reduziu a migração e a invasão das...

The activation of beta 2 adrenergic receptor (β2-AR), by chemical mediators of stress, can induce stimulatory or inhibitory effects on cell migration and invasion, depending on the type of malignancy. The importance of this receptor in the oral cancer outcome is not fully understood. The aim of this study was to verify β2- AR expression in oral squamous cell carcinoma cell lines (SCC-9 and SCC-25), and to investigate the role of activation of this receptor by norepinephrine and its blockade by an antagonist in migration and invasion of these neoplastic cells. SCC-9 and SCC-25 cells were investigated for gene and protein expression of β2-AR, respectively, by RT-qPCR and Western blot. The cell migration and invasion were analyzed by wound healing assay and Transwell invasion camera system, respectively. Different concentrations (0.1, 1 and 10μM) of norepinephrine were used to stimulate and 1μM propranolol was used to block the beta adrenergic receptors on cancer cells. Differences in mean values of the invasion and migration assays of SCC-9 and SCC-25 and β2-AR protein expression were compared by the Student t test with 5% significance level. The results showed that β2-AR gene and protein expression was verified in both oral cancer cell lines. The concentration of 10μM of norepinephrine inhibited significantly (p≤0.05), cell migration and invasion of SCC-9 and SCC-25, being the most pronounced effect in SCC-25 cells. Furthermore, there was a significant reduction (p≤0.05) of norepinephrine effect on cell migration when the β2-AR was inhibited by propranolol. In addition, blockade of β-ARs by propranolol partially reversed the effect of norepinephrine on the invasiveness of SCC-9 and SCC-25. These results show that norepinephrine via β2-AR activation, reduced the migration and invasion of oral squamous cell carcinoma cells and, therefore, the use of beta-adrenergic receptors agonists could become an adjuvant therapeutic target in the treatment of this malignancy.