ABSTRACT
ABSTRACT Introduction: Meningiomas are the most common intracranial tumors in adults. One of the mechanisms used by tumor cells to escape death by immune cells is to interfere with immunological checkpoints, thereby preventing the establishment of adequate immune response. Following this concept, a promising target for an immunomodulatory therapy is blocking programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1 axis), which is known to be crucial for immune escape mechanisms. Interferon-gamma (IFN-γ) is related to PD-L1 expression, produced by activated T cells, and may promote hyper-regulation of PD-L1 expression in tumor cells. Methods: The retrospective cross-sectional cohort study analyzed 93 patients diagnosed with meningioma of different degrees, and immunohistochemical reactions of PD-L1 and IFN-γ proteins were performed. Results: This study did not detect PD-L1 immunoexpression in any of the 93 analyzed cases. The PD-L1 expression in meningioma cells and their potential role in local immunosuppression are not fully established and their indication for anti-PD-L1 therapy as an alternative treatment for meningiomas is still controversial. Conclusion: IFN-γ immunoexpression was related to lower rates of tumor recurrence and longer progression-free survival time; there was also a relationship with the absence of pleomorphism, better differentiation and lower tumor grade for this marker.
RESUMEN Introducción: Los meningiomas son los tumores intracraneales más comunes en personas adultas. Uno de los mecanismos utilizados por células tumorales para escapar de la muerte es interferir con los puntos de control inmunológicos, impidiendo así el establecimiento de una respuesta inmunitaria adecuada. Siguiendo este concepto, un objetivo prometedor para una terapia inmunomoduladora es el bloqueo del eje de la proteína de muerte celular programada 1 (PD-1)/ligando 1 de muerte celular programada (PD-L1), que es conocido por ser crucial para los mecanismos de escape inmune. El interferón gamma (IFN-γ) se relaciona con la expresión de PD-L1, es producido por células T activadas y puede promover la hiperregulación de la expresión de PD-L1 en células tumorales. Métodos: El estudio de cohorte transversal retrospectivo analizó a 93 pacientes diagnosticados con meningioma de grados variables; se realizaron reacciones inmunohistoquímicas de las proteínas PD-L1 y del IFN-γ. Resultados: Este estudio no detectó inmunoexpresión de PD-L1 en ningún de los 93 casos analizados. La expresión de PD-L1 en células de meningioma y su función potencial en la inmunosupresión local no están totalmente establecidas, y su indicación de terapia anti-PD-L1 como tratamiento alternativo para meningiomas aún es controvertida. Conclusión: La inmunoexpresión de IFN-γ se relacionó con bajas tasas de recidiva tumoral y más tiempo de supervivencia libre de enfermedad, y se constató relación con ausencia de pleomorfismo, mejor diferenciación y grado tumoral más bajo para este marcador.
RESUMO Introdução: Os meningiomas são os tumores intracranianos mais comuns em adultos. Um dos mecanismos utilizados por células tumorais para escapar da morte por células imunes é interferir em checkpoints imunológicos, impedindo, assim, o estabelecimento de resposta imune adequada. Seguindo esse conceito, um alvo promissor para uma terapia imunomoduladora é o bloqueio do eixo de morte celular programada 1 (PD-1)/ligante de morte celular programada 1 (PD-L1), conhecido por ser crucial para mecanismos de escape imune. O interferon gama (IFN-γ) se relaciona com a expressão de PD-L1, sendo produzido por células T ativadas; pode promover a hiper-regulação da expressão de PD-L1 em células tumorais. Métodos: Estudo de coorte transversal retrospectivo que analisou 93 pacientes diagnosticados com meningioma de diversos graus. Reações imuno-histoquímicas das proteínas PD-L1 e do IFN-γ foram realizadas. Resultados: Este estudo não detectou imunoexpressão de PD-L1 em nenhum dos 93 casos analisados. A expressão de PD-L1 em células de meningioma e seu papel potencial na imunossupressão local não estão totalmente estabelecidos, e a indicação de terapia anti-PD-L1 como tratamento alternativo para meningiomas ainda é controversa. Conclusão: A imunoexpressão de IFN-γ relacionou-se com menores taxas de recidiva tumoral e maior tempo de sobrevida livre de progressão de doença. Constatou-se ainda relação com ausência de pleomorfismo, melhor diferenciação e menor grau tumoral para este marcador.
ABSTRACT
The study evaluates the clinical and pathological findings of 16 patients with locally advanced penile carcinoma (PC) submitted to emasculation, and discusses questions related to the usefulness of bilateral orchiectomy. Between 1999 and 2010, 172 patients with PC were treated. Sixteen (9%) underwent emasculation. Data were retrieved from the institution's database including age, ethnicity, date of surgery, residential setting, level of schooling, time to diagnosis, type of reconstruction, complications, tumor stage and grade, vascular and perineural invasion along with invasion of corpus cavernosum, corpus spongiosum, testicles, scrotum and urethra. A total of 16 patients (average: 63.1 years) with locally advanced PC were included. All were illiterate or semiliterate rural dwellers and 87% were white. The time to diagnosis was 8-12 months. The mean follow-up time was 31.9 months (1-119). By the time of the last follow-up, only seven patients (43.75%) were alive. Tumors were pT4 (n = 6), pT3 (n = 8), pT2 (n = 2), Grade I (n = 5) and Grade II (n = 11). The histopathological examination revealed invasion of the urethra (n = 13), scrotum (n = 5) and testicles (n = 1). The surgical margin was positive in one patient. Six patients (37.5%) had vascular invasion and 11 (68.7%) had perineural invasion. Currently, only one of the former is alive. The finding of focal microscopic testicular infiltration in only one of 32 testicles, even in the presence of clinically apparent scrotal invasion, suggests that emasculation without bilateral orchiectomy is a safe treatment option for patients with locally advanced PC.