El gen Kras/Nras provee instrucciones para la producción de una proteína llamada Kras, parte de una vía de señalización intracelular RAS/MAPK. La mutación del Kras/Nras tiene implicancias pronósticas y terapéuticas en diversos tumores como el cáncer de colon. Se expresa entre el 30 y 50% de los casos, además existen algunas diferencias respecto a localización, edad y sexo.Objetivos. Analizar la prevalencia de la mutación Kras/Nras.Correlacionar la presencia de la mutación con el sexo, la edad y estudiar su asociación con la localización en los tumores colo-rectales.Material y métodos.Se estudiaron 79 biopsias en pacientes con cáncer colo-rectal durante el período 2014 -2017. Se analizó el perfil molecular de las muestras. La mutación del gen Kras/Nras se estudió mediante el kit Kras y Nras de Entrogen, para detectar alteraciones genéticas de los codones 12, 13, 59, 61, 117 y 146 . Los perfiles mutacionales se correlacionaron con edad, sexo y localización. Para el análisis estadístico se utilizó el software SPSS. Se obtuvo frecuencia porcentual de la mutación y se aplicaron tablas de contingencia para establecer la relación de la mutación KRAS/NRAS con las variables. Análisis estadístico no paramétrico (Prueba Chi-cuadrado) con un valor de p= 0,05 (CI 95%).Resultado El 32 % de la población presento la mutación Kras/Nras.La relación entre la presencia de la mutación y localización fue del 36% para el lado derecho y el 30% para el izquierdo, no se encontró significación estadística (p=0.57).La relación de la mutación y edad mostró mayor prevalencia en menores a 50 años. Con respecto al sexo la mutación no mostró diferencias. Ambas asociaciones no fueron estadísticamente significativas (p=0.95 y p=0.70 respectivamente).ConclusiónLos resultados mostraron una prevalencia de la mutación Kras/Nras, y su relación con la edad y sexo, comparable con los datos publicados en la población occidental.No hay en esta muestra prevalencia de la mutación en el lado derecho como se observa en otros estudios, probablemente debido el tamaño de esta muestra.
both with stage IV pathologies. The entire study population was evaluated for PDL-1 before starting treatment, by IHC. Results: We included 58 patients, 33 patients (57%) had lung cancer and 25 (43%) had other types of tumors. When analyzing the toxicities of both groups it was observed that, the patients with lung cancer showed: Asthenia 20 patients (44%), Skin Rash 8 patients (18%), Diarrhea 3 patients (7%), hypothyroidism 2 patients (5%), liver toxicity 6 patients (13%) and hematological toxicity 6 patients (13%). In the second group patients exhibited: Asthenia 17 patients (61%), Skin Rash 4 patients (14%), Diarrhea 2 patients (7%), hypothyroidism 2 patients (7%) and hematological toxicity 3 patients (11%). Conclusion: In this work, we can observe that in both groups there were expected toxicities. The most frequent one was asthenia, but the group with lung cancer showed greater hepatic and hematological toxicity with a significant difference compared to other tumors.
Background: ALK activation is generally produced due to formation of fusion genes involving EML4, being described in 3 to 10% of NSCLC. ALK+ tumors present more frequently in young, non smoker patients, with female predominance and are generally adenocarcinomas. ALK alterations have been described in all clinical and pathologic subtypes and these should not be the sole indicators to search for the fusion. This determination describes a subgroup with different biological behavior and effective directed therapy. The ALK Break Apart FISH Probe Kit (Abbott Molecular, Des Plaines, IL) and the VENTANA ALK (D5F3) CDx Assay has become an FDA-approved companion diagnostic for targeted therapy. The FISH assay is fraught with technical challenges; including FISH signal instability and scoring difficulties. Consequently, the assay is prone to false negatives and false positives. Two case reports are presented with different diagnostic results in ALK status by IHC and FISH and diverse clinical responses to directed therapy. Method: ALK IHC testing was performed using the Ventana anti-ALK (D5F3) Rabbit monoclonal antibody (Roche, CE-IVD) used in combination with the OptiView DAB IHC Detection kit and OptiView Amplification Kit as a fully automated IHC assay on the Ventana BenchMark XT automated slide stainer. ALK FISH testing was performed using the Vysis ALK Break Apart Probe kit (2p23/ALK translocation detection, Abbott, CE-IVD). Results: We examined 308 NSCLC cases and compared the FISH results to ALK IHC. Of 8 (3%) cases identified as positive expression, only 6 have ALK rearrangement. Case 1: 54 years old male, 30 pack/year smoker, evaluated in October 2015 presenting fever and cough. CT
Background: Histopathological distinction between non-small cell lung cancer subtypes is still relevant in the age of targeted therapy due to the relatively low number of patients with actionable molecular alterations such as EGFR mutations or ALK rearrangements in squamous cell carcinomas. In addition, for patients without these alterations, the choice of most effective chemotherapy regimens is often based upon non-squamous vs squamous cell histology. However, histopathology scoring typically requires resected or biopsied tissue to be fixed, sliced, stained, and subjectively scored by a pathologist. Here we endeavor to demonstrate that subtle variances in gene expression within NSCLC patient samples can be used to classify the cancer subtype with a high degree of accuracy to pathology classification. Method: RNA extracted from 46 resected NSCLC cases (34 stage IIA/B, 12 stage IIIA/B; primarily adenocarcinomas and squamous cell carcinomas) were profiled using a transcriptome microarray platform (Illumina) and analyzed and compared to normal tissue using several Bioconductor R package pathway analysis tools and DAVID Bioinformatics Resources 6.8. Expression profiles were grouped by principle component score in a blinded manner. Result: Clustering samples based on the top 10% most variable genes resulted in a highly accurate separation of adenocarcinoma samples and squamous cell carcinoma samples, with only one case of squamous cell carcinoma being misclassified as adenocarcinoma. The altered pathways that differentiated these samples included p53 signalling and PI3K-Akt signaling pathways, Cell adhesion molecules (CAM), ECM-receptor interactions, Wnt signalling and several other key pathways. Conclusion: Due to the successes of targeted therapeutic approaches, evaluating patient biopsies or other samples for EFGR mutations and ALK rearrangements are currently the standard of care for advanced-stage NSCLC. Immunohistochemical staining for the purposes of subtyping NSCLC can aid in developing treatment strategies for patients without these molecular alterations, but this can significantly reduce the quantity of tissue available for subsequent molecular tests. Based on our data, we believe that expression variances in a relatively small pool of genes and pathway analysis is sufficient to accurately predict the subtype of NSCLC, or at least narrow the number of cases requiring input from a pathologist to a small number of more difficult cases.Background: Substantial advances have been made in the understanding of the biology of NSCLC in relation to the characterization of molecular abnormalities such as activations of oncogenes by mutations, translocations and amplifications, which are being used as molecular targets and predictive biomarkers. Molecular analysis of NSCLC, adeno carcinoma (AC) is now the standard of care for therapy selection Method: We determined the frequency of molecular alterations in EGFR and gene fusion ALK in our Caucasian and Hispanic populations
Background: Anti-programmed cell death (PD)-1 antibody therapies have shown durable clinical efficacy and manageable toxicity profiles, and have become a standard therapy in advanced non-small cell lung cancer (NSCLC). Because of manageable toxicity profiles, extensive interest in the potential benefits of anti-PD-1 antibody has expanded to high-risk patients such as the elderly or poor performance status (PS) patients. Here, we aimed to investigate predictive markers for the efficacy of anti-PD-1 antibody in elderly patients and poor PS patients. Method: The medical records of 75 years old or PS2 NSCLC patients treated with anti-PD-1 antibody (e.g., nivolumab and pembrolizumab) at the National Cancer Center Japan between December 1, 2015, and May 31, 2018, were reviewed retrospectively. We evaluated the association between efficacy for anti-PD-1 antibody and gender, smoking status, histology, PD-ligand 1(PD-L1) expression on tumor cells, white blood cell counts, lymphocyte counts, albumin, lactate dehydrogenase, c-reactive protein, and serum vascular endothelial growth factor (VEGF). We divided patients into two groups with the median values. Result: A total of 235 patients with advanced NSCLC treated with anti-PD-1 antibody were reviewed. Of these patients, 31 patients were 75 years old, and 22 patients were PS2. The median PFS was 6.9 months in patients aged 75 years and 2.1 months in PS2 patients. Cox proportional hazard regression analysis showed that only the low-VEGF was significantly associated with longer PFS in patients aged 75 years (HR, 0.35; 95% CI, 0.13-0.88; P ¼ 0.025) and in PS2 patients (HR, 0.31; 95% CI, 0.10-0.85; P ¼ 0.023). The overall response rate of patients with low-VEGF was tend to be higher than that with high-VEGF among patients aged 75 years (43% vs. 20%; P ¼ 0.18) and PS2 patients (20% vs. 0%; P ¼ 0.084). Conclusion: Low-VEGF in patients aged 75 years and PS2 patients was associated with longer PFS. Serum VEGF may thus be a biomarker for the efficacy of anti-PD-1 antibody therapy.
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