Amparo Benito - Academia.edu (original) (raw)

Papers by Amparo Benito

Journal of Thoracic Oncology, Oct 1, 2019

Journal of Clinical Oncology, May 20, 2019

e20621 Background: Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overa... more e20621 Background: Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overall survival (OS) greater than 2 years, are less than 10% in most series. Classical prognosis factors include stage, weight loss and ECOG, but more information is missing in the literature. Recently, EGFR, ALK and ROS 1 population (less than 20%) reach OS longer than 2 years. Immunotherapy has demonstrated very promising results with more LS compared to chemotherapy in first and second line setting. In this study, we focused in the analysis of LS patients with advanced NSCLC EGFR wt (wild type) and ALK nt (non-translocated), defined as those with OS greater than 36 months, in 7 hospitals in Madrid. Methods: In this serie, first of all, we will try to make a clinical, histopathological characterization collecting data from clinical reports according to a previously defined information. In a second step, we will carry out a genetic analysis of these patient samples comparing to an opposite extreme short survivors (SS) samples (OS less than 9 months). Initially, we used a NGS method of RNA-seq technology to identify differentiating profiles of gene expression between the two opposite populations. And finally, we confirmed this preliminary profile by RT-PCR in the rest of samples. Results: Ninety-six patients were initially included. The majority were men, smokers or former with adenocarcinoma and ECOG 0- 1. We have obtained a differential transcriptome expression between samples from 6 LS and 6 SS, resulting 13 over-expressed and 42 down-expressed genes in LS comparing to SS transcriptome expression. Some of the genes involved in this initial profile belong to different cellular pathways: Secretin Receptor, Surfactant Protein, Trefoil Factor 1, Serpin Family, Ca-bindings Protein channel and Toll like Receptor family. Finally, we carried on by RT-PCR in 40 samples of SS and LS survivors and only four genes were significantly down-regulated in SS compared to LS in the multivariate analysis. These 4 genes were related to Surfactant Proteins: SFTPA1 (p = 0.023), SFTPA2 (p = 0.027), SFTPB (p = 0.02) and SFTPC (p = 0.047). Conclusions: We present a sequential genetic analysis of a LS population with NSCLC EGFR wt (wild type) and ALK nt (non-translocated), obtaining a differential RNA seq- and RT-PCR gene profile based on different surfactant proteins expression. A further confirmation in a larger sample is ongoing.

Journal of Clinical Oncology, May 20, 2018

e21128Background: Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overal... more e21128Background: Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overall survival (OS) greater than 2 years, are less than 10% in most series. Classical prognosis factors ...

Archivos De Bronconeumologia, Jun 1, 2023

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PubMed, Jan 5, 2000

P53 protein expression, synonymous to p53 gene mutation, is a common event in head and neck squam... more P53 protein expression, synonymous to p53 gene mutation, is a common event in head and neck squamous cell carcinoma (HNSCC). However, the correlation between p53 expression and clinico-pathologic parameters remains unclear. Primary tumors for analysis were obtained from 99 patients with HNSCC. The expression of p53 was analyzed with monoclonal D07 antibody (Dako Corp., Glostrup, Denmark). Seventy five percent of 79 valid cases expressed the protein. A correlation was found between alcohol intake and p53 expression. None of the other clinico-pathologic factors were associated to p53 expression. Our results suggest that p53 may be involved in the development of HNSCC. However its clinical significance is still not completely understood.

European Journal of Cancer, Feb 1, 2005

We measured the expression of the p53 nuclear protein and epidermal growth factor receptor (EGFR)... more We measured the expression of the p53 nuclear protein and epidermal growth factor receptor (EGFR) in 46 biopsy samples from patients with advanced head and neck cancer treated with induction combination chemotherapy of 5-fluorouracil, cisplatin, and paclitaxel. Tumour expression of p53 protein was analysed with the monoclonal D07 antibody and EGFR with monoclonal H11 antibody. The overall response, defined as complete (CR) and partial response (PR) rates to treatment, was 88%. p53 positive staining was significantly more frequent in patients who did not respond to the induction treatment. EGFR expression failed to show any correlation with the response rate. Multivariate analysis indicated that a tumour location in the oral cavity together with p53 expression combined with moderate-to-high EGFR staining were independent prognostic factors of a shorter disease-free survival (DFS). Location of the tumour in the oral cavity and EGFR expression had independent prognostic value for overall survival (OS). We conclude that the EGFR status and an oral cavity location of the tumour have independent prognostic value in patients with advanced head and neck carcinoma treated with induction chemotherapy. The p53 status appears to be a determinant of the tumour chemo-sensitivity in advanced head and neck squamous cell carcinoma (HNSCC). The presence in the tumour of a p53-positive stain and moderate-to-high staining of EGFR is associated with a shorter DFS and time to treatment failure (TTF) probably reflecting a more aggressive tumour phenotype.

Diagnostic Cytopathology, Feb 14, 2022

Secretory breast carcinoma is a rare neoplasm, histologically well-characterized, and secondary t... more Secretory breast carcinoma is a rare neoplasm, histologically well-characterized, and secondary to ETV6-NTRK3 gene fusion, whose cytological features are scarcely described in the literature. We report the case of a woman with a history of secretory breast carcinoma 8 years before, who presented a periareolar nodule. A recurrence was diagnosed by fine-needle aspiration based on the cytomorphological features and pan-TRK immunocytochemistry on the cell block, and the patient underwent a mastectomy. The histology and molecular studies performed on the surgical specimen (immunohistochemistry, FISH and NGS) confirmed the diagnosis. Cytological smears showed abundant epithelial cellularity, in groups and single cells. These cells showed moderate atypia, with abundant cytoplasm. We observed intracytoplasmic inclusions and extracellular metachromatic globules. Immunocytochemical and immunohistochemical studies showed a triple negative breast tumour. NTRK overexpression was demonstrated with immunocytochemistry against pan-TRK on the cell block, as well as with immunohistochemistry in the surgical specimen. NTRK3 rearrangement was proved by FISH. In the primary tumour and in the recurrence, we demonstrated ETV6-NTRK3 fusion by NGS. After conducting a literature review, we have found 26 articles describing the cytological features of secretory breast carcinoma in 33 patients. The smears were described as groups of epithelial cells with vacuolated cytoplasm, single signet ring cells and a globular extracellular secretion. In only two cases molecular confirmation of the diagnosis with ETV6-NTRK3 fusion was proven, although not in the cytological specimen, but in the subsequent biopsy. The distinct cytological features of secretory breast carcinoma can help in its diagnosis, thus guiding the molecular studies. This is the first reported case that proves TRK overexpression, as a fusion surrogate, in the cytological sample.

Chest, Feb 1, 2022

CASE PRESENTATION An 84-year-old man with an active smoking habit presented to the ED with dyspne... more CASE PRESENTATION An 84-year-old man with an active smoking habit presented to the ED with dyspnea, hemoptysis, and thick phlegm that was difficult to clear. He reported no weight loss, no fever, and no chest pain or dysphonia. He denied both international travel and previous contact with confirmed cases of TB or SARS-CoV-2. He had no known occupational exposures. The patient's personal history included a resolved complete atrioventricular block that required a permanent pacemaker, moderate-to-severe COPD, rheumatoid arthritis (treated with oral prednisone, 2.5 mg/d) and B-chronic lymphocytic leukemia (treated with methotrexate and prophylactic oral supplements of ferrous sulfate). Moreover, he was in medical follow up because of a peptic ulcer, atrophic gastritis, and colonic diverticulosis. The patient also had a history of thoracic surgery after an episode of acute mediastinitis from an odontogenic infection, which required ICU management and temporal tracheostomy.

Annals of Hematology, May 27, 2020

Acta Cytologica, 1999

Horseshoe kidney is a renal congenital anomaly. It is the result of the fusion of either upper or... more Horseshoe kidney is a renal congenital anomaly. It is the result of the fusion of either upper or lower poles of both kidneys, appearing as a horseshoe-shaped structure. This anomaly is very frequent: it can be found in about 1 of every 50-1,000 autopsies). Computed tomography performed routinely after pancreatitis in a 37-year-old female showed a retroperitoneal mass of uncertain origin. Fine needle aspiration cytology (FNAC) smears evidenced normal renal tissue. Urography confirmed the diagnosis of horseshoe kidney. This is the first reported case of horseshoe kidney diagnosed by FNAC. It demonstrates the utility of FNAC for diagnosis of retroperitoneal masses, especially if they are asymptomatic.

Revista Española de Patología, 2023

American Journal of Dermatopathology, Apr 1, 1999

Although cutaneous epidermal (infundibular) cysts are extremely common lesions, neoplastic transf... more Although cutaneous epidermal (infundibular) cysts are extremely common lesions, neoplastic transformation of their epithelium is quite rare. We describe a patient with a squamous cell carcinoma arising in the wall of an otherwise conventional epidermal cyst. In addition, we review the literature concluding that most of the previously reported cases may not correspond to this rare occurrence.

Actas Dermo-Sifiliográficas, 2004

Resumen Fundamento El carcinoma basocelular y el carcinoma espinocelular son los canceres cutaneo... more Resumen Fundamento El carcinoma basocelular y el carcinoma espinocelular son los canceres cutaneos primarios de estirpe no melanocitica mas frecuentes. La extirpacion quirurgica con margenes predeterminados constituye el tratamiento de eleccion en la mayoria de las ocasiones. Algunos autores han observado margenes quirurgicos histologicos positivos hasta en el 15,7 % del total de canceres cutaneos de estirpe no melanocitica extirpados. Objetivo Determinar la tasa global de margenes quirurgicos positivos y la tasa de margenes quirurgicos positivos por servicio implicado en el tratamiento quirurgico en una serie de 1.104 carcinomas, y analizar sus repercusiones sobre la atencion sanitaria de los pacientes en nuestra area de salud. Material y metodos Estudio retrospectivo de los informes histopatologicos con diagnostico histopatologico de carcinoma cutaneo primario de estirpe no melanocitica con margenes quirurgicos histologicos positivos durante el trienio 2000-2002. En estos informes se han valorado los siguientes parametros: a) los servicios que han intervenido en el tratamiento quirurgico; b) tipo y subtipo histologico de carcinoma; c) limite quirurgico invadido por la neoplasia especificando si es el lateral, profundo, o ambos, y d) localizacion anatomica del carcinoma. Resultados En dermatologia se extirparon 770 carcinomas de los cuales 60 casos (7,7 %) tenian los margenes positivos; en cirugia general se extirparon 304 carcinomas de los cuales 92 casos (30,2 %) mostraban margenes positivos y en atencion primaria se extirparon 18 carcinomas de los cuales ocho (44,4 %) tenian margenes positivos. Los carcinomas basocelulares fueron los carcinomas que con mayor frecuencia tenian margenes positivos (70 %). El margen quirurgico mas comunmente invadido fue el lateral (76,2 %) y la localizacion mas frecuente la cara (58 %). Conclusion La tasa de carcinomas con margenes quirurgicos histologicos positivos en el servicio de dermatologia es inferior a la descrita por otros autores y muy inferior a la observada en los servicios no dermatologicos de nuestra area de salud (cirugia general y atencion primaria). La necesidad de reintervencion quirurgica en gran numero de estos carcinomas con margenes positivos reincorpora a los pacientes a la ya larga lista de espera quirurgica para estas lesiones cutaneas en nuestra area de salud y aumenta la demora de su tratamiento definitivo.

Future Oncology, Apr 1, 2021

Canakinumab is a human IgGκ monoclonal antibody, with high affinity and specificity for IL-1β. Th... more Canakinumab is a human IgGκ monoclonal antibody, with high affinity and specificity for IL-1β. The Canakinumab Anti-Inflammatory Thrombosis Outcome Study (CANTOS) trial, evaluating canakinumab for cardiovascular disease, provided the first signal of the potential of IL-1β inhibition on lung cancer incidence reduction. Here, we describe the rationale and design for CANOPY-N, a randomized Phase II trial evaluating IL-1β inhibition with or without immune checkpoint inhibition as neoadjuvant treatment in patients with non-small-cell lung cancer. Patients with stage IB to IIIA non-small-cell lung cancer eligible for complete resection will receive canakinumab or pembrolizumab as monotherapy, or in combination. The primary end point is major pathological response by central review; secondary end points include overall response rate, major pathological response (local review), surgical feasibility rate and pharmacokinetics. Clinical trial registration: NCT03968419 (ClinicalTrials.gov) Lay abstract: A previous study showed that canakinumab reduced the risk of lung cancer in patients with heart disease. Canakinumab blocks an inflammatory protein called IL-1β that is involved in cancer. Anticancer drugs used before surgery ('neo-adjuvant') can improve the success rate of surgery and may help prevent the cancer from returning. Neo-adjuvant trials help us understand how the drugs work and how they affect cancer. CANOPY-N (NCT03968419) is an ongoing randomized, exploratory, Phase II clinical trial testing canakinumab and pembrolizumab (a different cancer immunotherapy), alone or combined, for patients with early non-small-cell lung cancer. The study will test whether treatment can kill most cancer cells in the surgery sample ('major pathological response'). It will also investigate other effects on cancer biology, levels of molecules that measure possible clinical benefit ('biomarkers') and side effects.

Journal of Thoracic Oncology, Oct 1, 2021

Clinical Lung Cancer, Jul 1, 2019

Radon is the first cause of lung cancer in non-smokers by the WHO, which recommends not exceeding... more Radon is the first cause of lung cancer in non-smokers by the WHO, which recommends not exceeding 100Bq/m 3 in homes No risk factor has been identified yet for NSCLC harboring driver alterations, mainly non-smokers We showed median concentration of Bq/m , above the WHO-recommendation in EGFR-mutated, BRAF-mutated and ALK-rearranged NSCLC patients, with no differences between them ABSTRACT Background: Radon gas is the leading cause of lung cancer in the non-smoking population. The World Health Organization (WHO) recommends indoor concentrations <100 Bq/m 3. Several molecular alterations have recently been described in non-small cell lung cancer (NSCLC), mainly in non-smokers, with no risk factors identified. We studied the role of indoor radon in NSCLC patients harboring specific driver alterations. Patients and methods: We assessed the radon concentration from EGFR-, BRAF-mutated (m) and ALK-rearranged (r) NSCLC patients measured by an alpha-track detector placed in their homes, between September 2014 and August 2015. Clinical characteristics were collected prospectively, and pathology samples were reviewed retrospectively. Results: Forty-eight patients were included (36 EGFRm; 10 ALKr; 2 BRAFm). Median radon concentration was 104 Bq/m 3 (IQR 69-160) overall, and was 96 Bq/m3 (42-915) for EGFRm, 116 (64-852) for ALKr and 125 for BRAFm, with no significant differences. Twenty-seven patients (56%) had indoor radon above WHO recommendations, 8/10 (80%) ALKr, 2/2 (100%) BRAFm, 17/36 (47%) EGFRm. Conclusion: The median indoor radon concentration was above the WHO recommendation, with no differences between EGFR, ALK and BRAF patients. Concentrations above the WHO recommendations were most common with ALKr and BRAFm. These findings should be validated in larger studies.

American Journal of Dermatopathology, Dec 1, 1998

Journal of Thoracic Oncology, 2017

Expert Review of Molecular Diagnostics, May 4, 2021

Introduction: The development of several ROS1 inhibitors means that the importance of accurately ... more Introduction: The development of several ROS1 inhibitors means that the importance of accurately identifying ROS1-positive lung cancer patients has never been greater. Therefore, it is crucial that ROS1 testing assays become more standardized. Areas covered: Based on primary literature, combined with personal diagnostic and research experience, this review provide a pragmatic update on the use of the recently released VENTANA ROS1 (SP384) Rabbit Monoclonal Primary Antibody. Expert opinion: This assay provides high sensitivity, so it is an excellent analytical option when screening for ROS1 fusions in patients with advanced non-small cell lung carcinomas.

Cancer biology and medicine, 2020

Objective: Long-term survivors (LS) of non-small cell lung cancer (NSCLC) without driver alterati... more Objective: Long-term survivors (LS) of non-small cell lung cancer (NSCLC) without driver alterations, displaying an overall survival (OS) of more than 3 years, comprise around 10% of cases in several series treated with chemotherapy. There are classical prognosis factors for these cases [stage, Eastern Cooperative Oncology Group (ECOG), etc.], but more data are required in the literature. In this multi-center study, we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular characterization. Methods: In the first step, we conducted a clinical-pathological characterization of the patients. Afterwards, we carried out a genetic analysis by comparing LS to a sample of short-term survivors (SS) (with an OS less than 9 months). We initially used whole-genome RNA-seq to identify differentiating profiles of LS and SS, and later confirmed these with reverse transcription-polymerase chain reaction (RT-PCR) for the rest of the samples. Results: A total of 94 patients were included, who were mainly men, former smokers, having adenocarcinoma (AC)-type NSCLC with an ECOG of 0-1. We obtained an initial differential transcriptome expression, displaying 5 over-and 33 under-expressed genes involved in different pathways: namely, the secretin receptor, surfactant protein, trefoil factor 1 (TFF1), serpin, Ca-channels, and Tolllike receptor (TLRs) families. Finally, RT-PCR analysis of 40 (20 LS/20 SS) samples confirmed that four genes (surfactant proteins and SFTP) were significantly down-regulated in SS compared to LS by using an analysis of covariance (ANCOVA) model: SFTPA1 (P = 0.023), SFTPA2 (P = 0.027), SFTPB (P = 0.02), and SFTPC (P = 0.047). Conclusions: We present a sequential genetic analysis of a sample of NSCLC LS with no driver alterations, obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.