Aldehyde dehydrogenase isoform 1 (ALDH1) expression as a predictor of radiosensitivity in laryngeal cancer.

BACKGROUND: Aldehyde dehydrogenase isoform 1 (ALDH1) has been shown to be a marker of cancer stem cells (CSCs). These stem cells may be responsible for tumour perpetuation as well as local and distant invasion. Several studies have shown that CSCs are more chemoradiotherapy (CRT)-resistant and may be responsible for tumour recurrence. Other studies, in contrast, have found ALDH1 expression to be indicative of a better prognosis. METHODS: We retrospectively evaluated 84 patients diagnosed and treated for laryngeal cancer between 2006 and 2011. All patients underwent curative-intent radiotherapy or CRT at our institution. 57 of the 84 tumour samples contained sufficient material for ALDH1 assessment. RESULTS: ALDH1 expression was detected in 17.5 % (10/57) of the tissue samples. None of the tumours from stage I patients tested positive for ALDH1. The relapse rate in ALDH1 + patients was 10 versus 51.2 % for ALDH1-. No differences in overall survival were observed between the groups; however, disease-free survival was 90 % for the ALDH1 + group versus 48.9 % for ALDH1- patients (p = 0.034). CONCLUSION: The patients in this study with ALDH1 + tumours had better outcomes than their counterparts with ALDH1- tumours. This finding suggests that not all CSCs are resistant to conventional cancer treatments. It may also imply that new methods of correctly identifying these cells are needed.

Expresión de ciclo-oxigenasa 2 en carcinoma de laringe / Cyclooxigenase-2 expression in laryngeal carcinoma

Introducción: La sobrevida de carcinoma escamoso de laringe no ha aumentado significativamente en los últimos 20 años. Ciclo-oxigenasa 2 (COX-2) es una molécula que tiene un rol en la progresión tumoral ya que estimula la proliferación y angiogénesis e inhibe apoptosis celular. Objetivo: Evaluar la expresión de COX-2 en muestras de carcinoma escamoso de laringe. Material y método: Pacientes atendidos en los hospitales Barros Luco Trudeau y San Juan de Dios entre 2008 y 2011 con diagnóstico de carcinoma escamoso de laringe sin tratamiento previo. Se recolectaron tacos de biopsia los cuales fueron estudiados mediante inmunohistoquímica para la expresión de COX-2. Protocolo aprobado por Comité de Ética de la Facultad de Medicina de la Universidad de Chile. Resultados: Se incluyeron 32 casos. En 17 de ellos se describe sobreexpresión de COX-2, lo que equivale al 53% de la muestra. No hubo correlación con edad, sexo ni hábito tabáquico. Conclusión: La sobreexpresión de COX-2 es un fenómeno frecuente en carcinoma escamoso de laringe por lo cual es una molécula interesante para considerar como candidata a terapia adyuvante.

Introduction: Survival of laryngeal squamous cell carcinoma has not improved significantly in the last 20 years. Cyclooxigenase 2 (COX-2) has a role in carcinogenesis since it induces proliferation and angiogenesis, and inhibits apoptosis. Aim: To evaluate the expression of COX-2 in samples of laryngeal carcinoma. Material and methods: Patients attending Hospital San Juan de Dios and Barros Luco-Trudeau with diagnose of laryngeal carcinoma between 2008 and 2011 were included. Formalin fixed paraffin embedded samples were collected and COX-2 expression was assayed with immunohistochemistry. The study was approved by the ethics committee of Facultad de Medicina Universidad de Chile, and all patients consented. Results: 32 cases were included. COX-2 was overexpressed in 17, that is 53%. No correlation was identified with age, sex, or smoking habit. Conclusion: COX-2 overexpression is a frequent phenomenon in laryngeal carcinoma.

Expressions of Src homology 2 domain-containing phosphatase and its clinical significance in laryngeal carcinoma.

We investigated the expression of Src homology 2 domain-containing phosphatase (SHP-2) in laryngeal carcinoma and its clinical significance. Expression of SHP-2 was detected by immunohistochemical staining in normal mucosal tissues and various grades of laryngeal carcinoma. We looked for possible correlations between expression of SHP-2 in laryngeal carcinoma and clinical staging and lymph node metastasis. Immunochemical staining results revealed that the SHP-2 expression was significantly higher (88.24%) in laryngeal carcinoma than in normal mucosal tissue (25%). Additionally, the expression of SHP-2 was significantly correlated with lymph node metastasis, but not with clinical stage and gender of patients with laryngeal carcinoma. Therefore, SHP-2 may be useful as a prognostic marker for laryngeal carcinoma and as a therapeutic target in laryngeal carcinoma treatment.

Frecuencia de los polimorfismos CYP1A1*2A y deleción del gen GSTM1 en pacientes con carcinoma de células escamosas de laringe en relación al hábito tabáquico: estudio piloto en Chile / Frequency of CYP1A1*2A and GSTM1 gene polymorphisms in Chilean patients with squamous cell carcinoma of the larynx in relation to smoking habit: a pilot study

Introducción: Entre los factores de riesgo para cáncer laríngeo (CL) son relevantes el consumo de tabaco y alcohol. Estos xenobióticos son metabolizados por un grupo de enzimas, entre las cuales están CYP1A1 y GSTM1, cuyas variantes polimórficas se postulan como factores de riesgo para esta enfermedad. Objetivos: Describir la frecuencia de las variantes de los polimorfismos de CYP1A1 y GSTM1 en un grupo de pacientes diagnosticados con CL. Analizar la posible correlación entre las variantes genéticas de ambas enzimas y la presencia de CL. Evaluar la influencia del hábito tabáquico en el riesgo de aparición de cáncer escamoso de laringe en pacientes con genotipos de riesgo. Material y método: Se seleccionaron 35 pacientes con CL entre los años 2000 y 2010 en Servicio de Otorrinolaringología del HBLT y 124 controles reclutados en el Centro de Investigaciones Farmacológicas y Toxicológicas (IFT). A todos los individuos se les registraron datos demográficos y extrajo una muestra de sangre para analizar las variantes polimórficas de CYP1A1 y GSTM1, mediante PCR-RFLP. Resultados: De un total de 35pacientes 54,3% presentan el genotipo GSTM1 (-/-) y 17,1% el genotipo CYP1A1*2A C/C. En el grupo control (n =140) estas frecuencias fueron de 19,35°% y 10,48%o, respectivamente. Se observó una correlación entre GSTM1 y el CL, estratificado por el hábito tabáquico y alcohólico. No se encontraron relaciones estadísticamente significativas con el hábito alcohólico y/o tabáquico. No se observaron asociaciones entre la patología y la combinación de genotipos o entre genotipos y el hábito tabáquico o alcohólico. Conclusiones: Los resultados muestran una asociación estadísticamente significativa entre la deleción de GSTM1 (-/-) y el riesgo de presentar CL, lo que refleja el importante papel que juega esta enzima en la desintoxicación de compuestos cancerígenos. Sin embargo, se requiere incrementar el número de pacientes para establecer apropiadamente la relación genético-ambiental que permite adjudicar un papel relevante a estos biomarcadores.

Introduction: Tobacco and alcohol consumption are recognized risk factors for squamous cell carcinoma of the larynx. These xenobiotics are metabolized by numerous enzymes, among which, CYP1A1 and GSTM1 gene polymorphisms have been identified as risk factors for developing tobacco related cancers as lung and laryngeal carcinomas. Nevertheless, these polymorphisms have not been studied in Chilean patients with squamous cell carcinoma of the larynx. Aim: To describe, for the first time, the frequency of CYP1A1 and GSTM1 gene polymorphisms in Chilean patients with squamous cell carcinoma of the larynx. Material and method: We conducted a case-control study. The case group consisted of 35 Chilean patients with squamous cell carcinoma of the larynx; the control group was formed by 124 Chilean subjects without cancer diagnosis. Demographic data as age, sex and quantification of tobacco smoking and alcohol consumption were recorded in all individuals. CYP1A1 and GSTM1 gene polymorphisms were evaluated by polymerase chain reaction and restriction enzymes (PCR-RFLP). Results: The frequency of CYP1A1*2A C/C genotype was 54, 3°% among laryngeal cancerpatients and 17,1%% among control subjects. The frequency ofGSTM1 (-/-) genotype was 19,35 %% among laryngeal cancer patients and 10,48%% among control subjects. There were no statistically significant relationships between this gene polymorphisms and tobacco smoking or alcohol consumption. There were no associations between the presence of both gene polymorphisms in the same individual and the presence of laryngeal cancer. Interestingly we found an OR of 8.69 (CI 2.90 to 26.01) for GSTM1 (-/-) polymorphism and laryngeal cancer, stratified by tobacco smoking and alcohol consumption. Conclusions: Our work shows that the deletion of GSTM1 could be an important risk factor for squamous cell carcinoma of the larynx in Chilean patients. This finding reflects the important role that detoxification of carcinogenic compounds plays in Chilean population. However, it is necessary to increase the number of studied patients to properly establish the genetic-environmental relationship ascribed to these biomarkers.

Interaction between CYP 2C19*3 polymorphism and smoking in relation to laryngeal carcinoma in the Chinese Han population.

Cytochrome P450 (CYP) 2C19 metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids, which strongly promote proliferation of cancer cells in vitro and in vivo. Knowing that smoking is the most important risk factor for laryngeal carcinoma, we examined the relationships between CYP2C19*3 polymorphism, smoking and laryngeal carcinoma in the Chinese Han population. In a Chinese Han case-control study of 300 laryngeal carcinoma patients and 300 healthy controls, we investigated polymorphism in the CYP2C19 gene by PCR-RFLP analysis. The CYP2C19*3 AG + AA genotype was significantly more prevalent in laryngeal carcinoma patients (6.67 vs 2.67%; P = 0.02). Multiple logistic regression analysis showed smoking (odds ratio (OR) = 6.353, 95% confidence interval (CI) = 4.413-9.144; P < 0.001) and alcohol consumption (OR = 2.607, 95%CI = 1.130-6.016; P = 0.025) as independent risk factors for laryngeal carcinoma; there was a significant interaction between CYP2C19*3 and smoking (OR = 17.842, 95%CI = 13.32-31.102; P = 0.009). We conclude that CYP2C19*3 polymorphism is significantly associated with laryngeal carcinoma in the Chinese Han population.