The Distinctive Features behind the Aggressiveness of Oral and Cutaneous Squamous Cell Carcinomas

Squamous cell carcinomas arise from stratified squamous epithelia. Here, a comparative analysis based on recent studies defining the genetic alterations and composition of the stroma of oral and cutaneous squamous cell carcinomas (OSCC and CSCC, respectively) was performed. Both carcinomas share some but not all histological and genetic features. This review was focused on how mutations in tumor suppressor genes and protooncogenes cooperate to determine the differentiation, aggressiveness, and metastatic potential of OSCC and CSCC. In fact, driver mutations in tumor suppressor genes are more frequently observed in OSCC than CSCC. These include mutations in TP53 (encoding pP53 protein), CDKN2A (encoding cyclin dependent kinase inhibitor 2A), FAT1 (encoding FAT atypical cadherin 1), and KMT2D (encoding lysine methyltransferase 2D), with the exception of NOTCH (encoding Notch receptor 1), whose mutation frequency is lower in OSCC compared to CSCC. Finally, we describe the differential composition of the tumor microenvironment and how this influences the aggressiveness of each tumor type. Although both OSCC and CSCC tumors are highly infiltrated by immune cells, high levels of tumor-infiltrating lymphocytes (TILs) have been more frequently reported as predictors of better outcomes in OSCC than CSCC. In conclusion, OSCC and CSCC partially share genetic alterations and possess different causal factors triggering their development. The tumor microenvironment plays a key role determining the outcome of the disease.Instituto de Salud Carlos IIIMinisterio de economía y competitividad (España)Depto. de MedicinaFac. de MedicinaTRUEpubDescuento UC

The Distinctive Features behind the Aggressiveness of Oral and Cutaneous Squamous Cell Carcinomas

Squamous cell carcinomas arise from stratified squamous epithelia. Here, a comparative analysis based on recent studies defining the genetic alterations and composition of the stroma of oral and cutaneous squamous cell carcinomas (OSCC and CSCC, respectively) was performed. Both carcinomas share some but not all histological and genetic features. This review was focused on how mutations in tumor suppressor genes and protooncogenes cooperate to determine the differentiation, aggressiveness, and metastatic potential of OSCC and CSCC. In fact, driver mutations in tumor suppressor genes are more frequently observed in OSCC than CSCC. These include mutations in TP53 (encoding pP53 protein), CDKN2A (encoding cyclin dependent kinase inhibitor 2A), FAT1 (encoding FAT atypical cadherin 1), and KMT2D (encoding lysine methyltransferase 2D), with the exception of NOTCH (encoding Notch receptor 1), whose mutation frequency is lower in OSCC compared to CSCC. Finally, we describe the differential composition of the tumor microenvironment and how this influences the aggressiveness of each tumor type. Although both OSCC and CSCC tumors are highly infiltrated by immune cells, high levels of tumor-infiltrating lymphocytes (TILs) have been more frequently reported as predictors of better outcomes in OSCC than CSCC. In conclusion, OSCC and CSCC partially share genetic alterations and possess different causal factors triggering their development. The tumor microenvironment plays a key role determining the outcome of the disease

The Distinctive Features behind the Aggressiveness of Oral and Cutaneous Squamous Cell Carcinomas

Cursos de Formación de Postgrado; Número de subvención: UCM920547Squamous cell carcinomas arise from stratified squamous epithelia. Here, a comparative analysis based on recent studies defining the genetic alterations and composition of the stroma of oral and cutaneous squamous cell carcinomas (OSCC and CSCC, respectively) was performed. Both carcinomas share some but not all histological and genetic features. This review was focused on how mutations in tumor suppressor genes and protooncogenes cooperate to determine the differentiation, aggressiveness, and metastatic potential of OSCC and CSCC. In fact, driver mutations in tumor suppressor genes are more frequently observed in OSCC than CSCC. These include mutations in TP53 (encoding pP53 protein), CDKN2A (encoding cyclin dependent kinase inhibitor 2A), FAT1 (encoding FAT atypical cadherin 1), and KMT2D (encoding lysine methyltransferase 2D), with the exception of NOTCH (encoding Notch receptor 1), whose mutation frequency is lower in OSCC compared to CSCC. Finally, we describe the differential composition of the tumor microenvironment and how this influences the aggressiveness of each tumor type. Although both OSCC and CSCC tumors are highly infiltrated by immune cells, high levels of tumor-infiltrating lymphocytes (TILs) have been more frequently reported as predictors of better outcomes in OSCC than CSCC. In conclusion, OSCC and CSCC partially share genetic alterations and possess different causal factors triggering their development. The tumor microenvironment plays a key role determining the outcome of the disease.Instituto de Salud Carlos III (España)Depto. de CirugíaFac. de MedicinaTRUEpubDescuento UC

¿Está indicada la prescripción de antibióticos en la extracción del tercer molar retenido?: Estudio comparativo entre patrones de prescripción

Objetivo. Valorar si existe una diferencia significativa en tasa de infección tras cirugía de extracción dentaria en dos hospitales de Noruega y España, donde se aplican protocolos de profilaxis quirúrgica diferentes. Material y Métodos. Se realizó un estudio observacional analítico, tipo cohortes retrospectivo, analizando pacientes sanos, sin factores de riesgo, operados de tercer molar incluido en los servicios de maxilofacial de dos hospitales diferentes: St. Olav de Trondheim (Noruega) y Clínico San Carlos de Madrid (España). Se recogieron las variables: edad, número de piezas extraídas, tipo de anestesia, y observaciones recogidas en la historia clínica sobre el curso de la operación. Para valorar el desarrollo infección postoperatoria se recogieron los datos de los pacientes que escogieron el hospital como lugar de retirada de los puntos en el Hospital St. Olav, y en el Hospital Clínico San Carlos se llevó a cabo una encuesta telefónica para conocer el curso de la operación meses después. Resultados. El 11,1% de los pacientes operados en el Hospital St. Olav recibió pauta antibiótica durante una semana tras la operación, mientras que en el Hospital Clínico San Carlos fue del 100%. La tasa de infección tras ésta fue del 15% en el Hospital de St. Olav y del 7,5% en el Hospital Clínico siendo estas diferencias no estadísticamente significativas. Conclusiones. La administración sistemática de antibiótico a pacientes sanos sin factores de riesgo sometidos a extracción quirúrgica del tercer molar retenido es una práctica rutinaria en clínica que no parece estar justificada.Depto. de MedicinaFac. de MedicinaTRUEpu

Clinical Behavior, Mutational Profile and T-Cell Repertoire of High-Grade Neuroendocrine Tumors of the Head and Neck

Neuroendocrine carcinomas (NECs) of the head and neck (HN) account for n = 8 stage II/IVA/B, all received (chemo)radiotherapy with/without prior surgery or induction chemotherapy, with complete response in 7/8 (87.5%). Among n = 6 recurrent/metastatic patients, three received anti-PD1 (nivolumab (2), pembrolizumab (1)): two achieved partial responses lasting 24 and 10 months. After a median follow-up of 30 and 23.5 months since diagnosis and since recurrent/metastatic, median OS was not reached. Median TMB (n = 7) was 6.72 Mut/Mb. The most common pathogenic variants were TP53, HNF1A, SMARCB1, CDKN2A, PIK3CA, RB1 and MYC. There were 224 median TCR clones (n = 5 pts). In one patient, TCR clones increased from 59 to 1446 after nivolumab. HN NECs may achieve long-lasting survival with multimodality treatment. They harbor moderate-high TMBs and large TCR repertoires, which may explain responses to anti-PD1 agents in two patients and justify the study of immunotherapy in this disease