RESUMEN
Cancer will remain one of the most significant challenges for public health, locally and globally. Currently, cancer is the leading cause of death in our country. Thanks to the enormous knowledge accumulated in recent decades on the cellular and molecular bases of cancer, precision oncology has been developed, an approach that allows for increasingly precise pharmacological treatment based on diagnostic tests. Advanced technologies such as next-generation sequencing are used for this purpose. It is essential to implement these technologies in current and future health systems to optimize the arsenal of strategies for cancer control. This review discusses some of the achievements of precision oncology, particularly applied to solid tumors. It addresses the state-of-the-art minimum biomarkers required for the diagnosis of this important group of neoplasms, the local situation regarding technological capabilities installed in the national territory, either for research or diagnosis, and the potential health impact of applying all this practical knowledge to serve people with cancer, both in the public and private sectors.
Asunto(s)
Neoplasias , Medicina de Precisión , Humanos , Chile , Neoplasias/diagnóstico , Neoplasias/genética , Medicina de Precisión/métodos , Biomarcadores de Tumor/genética , Técnicas de Diagnóstico Molecular/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Oncología Médica/tendencias , Oncología Médica/métodosRESUMEN
BACKGROUND: Breast cancer incidence is increasing rapidly in Latin America, with a higher proportion of cases among young women than in developed countries. Studies have linked inflammation to breast cancer development, but data is limited in premenopausal women, especially in Latin America. METHODS: We investigated the associations between serum biomarkers of chronic inflammation (interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), leptin, adiponectin) and risk of premenopausal breast cancer among 453 cases and 453 matched, population-based controls from Chile, Colombia, Costa Rica, and Mexico. Odds ratios (OR) were estimated using conditional logistic regression models. Analyses were stratified by size and hormonal receptor status of the tumors. RESULTS: IL-6 (ORper standard deviation (SD) = 1.33 (1.11-1.60)) and TNF-α (ORper SD = 1.32 (1.11-1.58)) were positively associated with breast cancer risk in fully adjusted models. Evidence of heterogeneity by estrogen receptor (ER) status was observed for IL-8 (P-homogeneity = 0.05), with a positive association in ER-negative tumors only. IL-8 (P-homogeneity = 0.06) and TNF-α (P-homogeneity = 0.003) were positively associated with risk in the largest tumors, while for leptin (P-homogeneity = 0.003) a positive association was observed for the smallest tumors only. CONCLUSIONS: The results of this study support the implication of chronic inflammation in breast cancer risk in young women in Latin America. Largest studies of prospective design are needed to confirm these findings in premenopausal women.
Asunto(s)
Neoplasias de la Mama , Biomarcadores , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Femenino , Humanos , Inflamación/complicaciones , Interleucina-6 , Interleucina-8 , América Latina/epidemiología , Leptina , Factores de Riesgo , Factor de Necrosis Tumoral alfaRESUMEN
Introduction: The incidence of squamous carcinoma of the oropharynx (OPSCC) has presented an increase worldwide, a fact that occurs along with a phenomenon of epidemiological transition, whose pathogenesis is linked to human papilloma virus (HPV) in a significant part of the cases. Published evidence at the Latin American level is scarce. The present study aims to evaluate the epidemiological and clinical characteristics of patients with oropharyngeal cancer treated in a public oncology reference centre in Chile. Methodology: A cross-sectional study was carried out. Patients with histological confirmation of OPSCC aged 18 years or older, referred to the National Cancer Institute of Chile between 2012 and 2023 were included. The association with HPV was determined by immunohistochemistry for p16. Results: 178 patients were analysed, most of them in locoregionally advanced stages involving the palatine tonsil. Seventy-seven percent were male, with a median age of 60 years. Sixty-seven percent of patients were positive for p16, with a progressive increase to 85% in the last 2 years of the study. The p16(+) patients were younger and had fewer classical risk factors. Primary treatment was radiotherapy in 94% of patients. Conclusion: The epidemiological profile of patients with OPSCC treated in a Chilean public oncology referral centre reflects the epidemiological transition observed in developed countries. This change justifies the need to adapt health policies and conduct research that considers the characteristics of this new epidemiological profile.
RESUMEN
El cáncer seguirá siendo uno de los mayores desafíos para la salud pública a nivel local y mundial. Actualmente, en nuestro país, el cáncer es la principal causa de muerte. Gracias al enorme conocimiento acumulado en las últimas décadas sobre las bases celulares y moleculares del cáncer, se ha desarrollado la oncología de precisión, un enfoque que permite dirigir de manera cada vez más precisa el tratamiento farmacológico en función de los exámenes de diagnóstico. Para ello se utilizan tecnologías avanzadas, como la secuenciación de próxima generación. Es imprescindible implementar estas tecnologías en los sistemas sanitarios actuales y futuros para optimizar el arsenal de estrategias para el control del cáncer. En esta revisión, se discuten algunos alcances de la oncología de precisión, especialmente aplicada a tumores sólidos. Se aborda el estado del arte de los biomarcadores mínimos necesarios para el diagnóstico de este importante grupo de neoplasias, la situación local en cuanto a las capacidades tecnológicas instaladas en el territorio nacional ya sea con fines de investigación o diagnóstico, y el potencial impacto sanitario que tendría la aplicación de todo este conocimiento práctico al servicio de las personas con cáncer, tanto en el sector público como privado.
Cancer will remain one of the most significant challenges for public health, locally and globally. Currently, cancer is the leading cause of death in our country. Thanks to the enormous knowledge accumulated in recent decades on the cellular and molecular bases of cancer, precision oncology has been developed, an approach that allows for increasingly precise pharmacological treatment based on diagnostic tests. Advanced technologies such as next-generation sequencing are used for this purpose. It is essential to implement these technologies in current and future health systems to optimize the arsenal of strategies for cancer control. This review discusses some of the achievements of precision oncology, particularly applied to solid tumors. It addresses the state-of-the-art minimum biomarkers required for the diagnosis of this important group of neoplasms, the local situation regarding technological capabilities installed in the national territory, either for research or diagnosis, and the potential health impact of applying all this practical knowledge to serve people with cancer, both in the public and private sectors.
RESUMEN
OBJECTIVES: To compare the expression of nerve growth factor (NGF) and its high-affinity receptor trkA in normal ovaries and in epithelial ovarian carcinomas. Given NGF acts as an angiogenic factor through a vascular endothelial growth factor (VEGF)-mediated mechanism in several types of tissues, we examined whether NGF regulates the expression of VEGF isoforms in epithelial ovarian cancer (EOC). METHODS: The expression and localization of NGF and tyrosine kinase receptor A (trkA) in normal ovarian samples and in ovarian cancer samples were analyzed by RT-PCR and immunohistochemistry. NGF regulates the expression of three VEGF isoforms (VEGF(121), VEGF(165) and VEGF(189)); these were examined using RT-PCR in explants of EOC and ELISA in culture media. RESULTS: TrkA mRNA levels were over-expressed in ovarian cancer compared to normal ovarian samples, whereas NGF mRNA levels remained unchanged. NGF and trkA proteins were absent or found in very low levels in normal ovarian surface epithelium (OSE), whereas they were highly expressed in epithelial cells of EOC. Additionally, NGF stimulated the expression of VEGF isoforms in cancer explants. The effect was dose-dependent and inhibited by a NGF antibody and by K(252a), a trk receptor inhibitor. CONCLUSION: The abundance of NGF and trkA receptors in epithelial cells of EOC, together with the ability of NGF to increase VEGF expression strongly suggests an autocrine role of NGF in EOC. These findings suggest that blocking neurotrophin action could be a therapeutic target in treating ovarian cancer.
Asunto(s)
Factor de Crecimiento Nervioso/metabolismo , Neoplasias Ováricas/metabolismo , Receptor trkA/metabolismo , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Adulto , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Factor de Crecimiento Nervioso/biosíntesis , Factor de Crecimiento Nervioso/genética , Neoplasias Ováricas/enzimología , Neoplasias Ováricas/genética , Ovario/enzimología , Ovario/metabolismo , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Receptor trkA/biosíntesis , Receptor trkA/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
The presence of cancer in a hernia sac is uncommon. The tumor can involve the hernia sac, the herniated mass or be external to the hernia sac. We report two cases with this condition. A 68 years old male was operated of a right inguinal hernia. During surgery, several white nodules were noted in the internal side of hernia sac. The same lesions were present in the mesentery. Pathological study revealed an adenocarcinoma. The primary tumor was not located and the patient died one and a half years after the procedure. A 62 years old male was operated due to an irreducible inguinal mass, seven months after a subtotal gastrectomy for gastric cancer. During the resection of the mass, metastasis implants in the mesenteric adipose tissue were noted. A mini laparotomy was performed and an extensive peritoneal tumor dissemination was found. The patient died two months after surgery.
Asunto(s)
Adenocarcinoma/secundario , Neoplasias del Colon/secundario , Hernia Inguinal/patología , Neoplasias Primarias Desconocidas , Neoplasias Gástricas/patología , Anciano , Resultado Fatal , Hernia Inguinal/cirugía , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/cirugíaRESUMEN
BACKGROUND: Follicular carcinomas account for 15% of thyroid malignant tumors. The differential diagnosis between adenoma and minimally invasive follicular carcinoma is difficult and lacks reproducibility especially in frozen sections. As the diagnosis depends on finding foci of capsular invasion, multiple sections must be examined. Numerous immunohistochemical markers have been studied for determining malignancy. AIM: To assess the efficacy of HBME-1 and Cyclin-D1 as diagnostic markers for follicular thyroid carcinoma. MATERIAL AND METHOD: We evaluated retrospectively 21 thyroidectomy specimens of 18 women and 3 men with diagnosis of adenoma or follicular carcinomas, both by hematoxylin and eosin stain and by immunohistochemistry using the avidin biotin method for the markers HBME-1 and Cyclin D1. RESULTS: The sensitivity and specificity of HBME-1 for the diagnosis of follicular thyroid carcinoma, were 88.9% and 100%, respectively whereas for Cyclin D1 the sensitivity and specificity were 22.2% and 100%, respectively. There were no false positive cases. CONCLUSIONS: HBME-1 has excellent sensitivity and specificity for the diagnosis of follicular carcinoma.
Asunto(s)
Adenocarcinoma Folicular/diagnóstico , Biomarcadores de Tumor/análisis , Ciclina D1/análisis , Neoplasias de la Tiroides/diagnóstico , Adenocarcinoma Folicular/química , Adenoma/química , Adenoma/diagnóstico , Adolescente , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Neoplasias de la Tiroides/químicaRESUMEN
BACKGROUND: Nodular thyroid disease is a very common disorder with a low frequency of malignancy. The most accurate diagnostic test is fine needle aspiration biopsy (FNAB) of nodules with cytological analysis of the sample. However, this procedure has some limitations in the diagnosis of follicular and papillary thyroid carcinoma. AIM: To detect mRNA from specific malignancy markers in thyroid nodules and to evaluate their potential correlation with cytological and pathological diagnosis. PATIENTS AND METHODS: In 20 patients with thyroid nodules FNAB was performed prior to surgery. The main part of the FNAB sample was used to perform classical cytology. In the remaining of the sample were detected MUC-1, CD26, galectin-3 and TSH receptor mRNAs by RT-PCR technique. RESULTS: Eight patients had positive cytology for papillary cancer, which was confirmed by pathology. Nine had suspicious or non conclusive cytological findings and 3 were negative for neoplastic cells; all 12 were pathologically benign. We detected TSH receptor and galectin-3 mRNA in almost all benign and malignant nodules. MUC-1 was present in 5/8 papillary carcinoma (62.5%), and 1/12 benign nodules (8.3%). CD26 was detected in 7/8 papillary carcinomas but also in 8/12 benign nodules. CONCLUSIONS: RT-PCR can be performed in very small samples of thyroid tissue to detect several mRNA markers. MUC-1 can be a potentially useful marker of malignancy in thyroid nodules. It can be detected by RT-PCR as a complementary technique in the diagnostic evaluation of thyroid nodules.
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Biomarcadores de Tumor/análisis , Carcinoma Papilar/química , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Nódulo Tiroideo/química , Biopsia con Aguja Fina , Carcinoma Papilar/patología , Electroforesis en Gel de Agar , Humanos , Estudios Prospectivos , ARN Mensajero/análisis , Nódulo Tiroideo/patologíaRESUMEN
We report a 78 year old male with prostatism, that was subjected to a prostate biopsy. The pathological study showed a microvascular lymphocytic infiltration. Four months later, the patients presented with reduced alertness, cough, dyspnea, fever and elevation of lactic dehydrogenase and erythrocyte sedimentation rate. Chest and abdominal CAT scans, bone marrow aspirate, protein electrophoresis and prostate specific antigen were normal. A re-evaluation of prostate biopsy showed an intravascular lymphoid infiltration, positive for CD45 and CD20, compatible with the diagnosis of intravascular lymphoma. Chemotherapy was started, but it was not tolerated by the patient and the response was partial. Therefore, treatment with monoclonal antibodies anti CD20 (Rituximab) was started. The tumor had a complete and prolonged (24 months) remission after the treatment
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Neoplasias Vasculares/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales de Origen Murino , Antígenos CD20/análisis , Biopsia , Humanos , Masculino , Hiperplasia Prostática/patología , Rituximab , Neoplasias Vasculares/patologíaRESUMEN
BACKGROUND: The urea breath test (UBT) with a microdose of [14C] is a non-invasive and simple method for the assessment of gastric infection by Helicobacter pylori. The aim of this study was to compare the [14C]UBT with invasive methods widely used for assessment of H. pylori gastric infection, including histology with hematoxylin-eosin staining, the gastric smear technique using Giemsa staining, and the biopsy urease test. MATERIAL/METHODS: We evaluated patients referred to our clinic for elective upper gastrointestinal endoscopy excluding those on antibiotics and/or bismuth during the previous 4 weeks, patients on H+ blockers or H2 antihistamines during the previous 7 days, pregnant women, and patients who had undergone gastric surgery or had bleeding disorders. Eighty-nine patients ranging in age from 18-75 years were included in the final study population, 61 women and 28 men (mean age: 43(15 years). RESULTS: When histology alone was considered as the reference standard, sensitivity for the [14 C]UBT was 94%, with a specificity of 37%; when the Giemsa technique, sensitivity was 95%, and specificity 35%; and when the biopsy urease test, sensitivity was 94% and specificity 45%. With two or more invasive techniques together considered as the reference standard, the [14C]UBT had a sensitivity of 95%, with a specificity of 44%. CONCLUSIONS: [14C]UBT is an objective and reproducible technique, capable of sampling the whole gastric mucosa. It shows high sensitivity, but low specificity, which could be explained by limited gastric sampling plus subjective interpretation in the invasive techniques that are currently used as gold standard.
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Pruebas Respiratorias/métodos , Radioisótopos de Carbono , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/metabolismo , Urea/metabolismo , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Embarazo , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estadística como Asunto , Urea/químicaRESUMEN
Introduction: Directional vacuum-assisted stereotactic breast biopsy (DVAB), represents an excellent method for obtaining pathological diagnosis, being in many cases an alternative to surgery. Objectives: To present our 2-year experience in DVAB at the University of Chile's Clinical Hospital. Materials and methods: a descriptive retrospective study of DVAB was conducted in our Hospital from March 2005 to November 2007. Morphology of lesions, BI-RADS classification, pathology reports, complications as well as epidemiological data were recorded. Results: We included 79 patients with 95 lesions. Mean age 55 years. Of the 95 biopsies, 95.7 percent were microcalcifications. The sensitivity was 92.8 percent and specificity 100 percent. The positive predictive value was 100 percent, while negative PVwas 98.7 percent, with 8 percent of subestimation and complication rate of 3,1 percent. Conclusions: Our results confirm the advantages of said procedure in our Center, proving DVAB as highly reliable, with good histological correlation and minimal complications.
Introducción: La biopsia estereotáxica digital mamaria (BED), representa un excelente método para obtener diagnóstico histológico, siendo alternativa de elección frente a la cirugía en muchos casos. Objetivo: Presentar nuestra experiencia en la aplicación de la BED en el Hospital Clínico de Universidad de Chile. Material y método: Estudio descriptivo, retrospectivo de BED realizadas en el Hospital Clínico de la Universidad de Chile (marzo 2005-noviembre 2007). Se registró morfología de las lesiones, clasificación BI-RADS, informes de anatomía patológica, complicaciones y datos epidemiológicos. Resultados: Se incluyó a 79 pacientes con 95 lesiones. Edad promedio 55 años. De las 95 biopsias, 95,7 por ciento correspondieron a microcalcificaciones. La sensibilidad fue 92,8 por ciento y la especificidad 100 por ciento. El valor predictivo positivo fue 100 por ciento y negativo 98,7 por ciento. La subestimación fue de 8 por ciento y la tasa de complicaciones 3,1 por ciento. Conclusiones: Nuestros resultados confirman las ventajas del procedimiento en nuestro Centro, demostrando la BED como altamente confiable, con buena correlación histológica y mínimas complicaciones.
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Humanos , Femenino , Adulto , Persona de Mediana Edad , Biopsia con Aguja/métodos , Enfermedades de la Mama/patología , Técnicas Estereotáxicas , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad , VacioRESUMEN
We report a 78 year old male with prostatism, that was subjected to a prostate biopsy. The pathological study showed a microvascular lymphocytic infiltration. Four months later, the patients presentd with reduced alertness, cough, dyspnea, fever and elevation of lactic dehydrogenase and erythrocyte sedimentation rate. Chest and abdominal CAT scans, bone marrow aspirate, protein electrophoresis and prostate specific antigen were normal. A re-evaluation of prostate biopsy showed an intravascular lymphoid infiltration, positive for CD45 and CD20, compatible with the diagnosis of intravascular lymphoma. Chemotherapy was started, but it was not tolerated by the patient and the response was partial. Therefore, treatment with monoclonal antibodies anti CD20 (Rituximab) was started. The tumor had a complete and prolonged (24 months) remission after the treatment.