Tania Labiano

Assessment of Epidermal Growth Factor Receptor and K-Ras Mutation Status in Cytological Stained Smears of Non-Small Cell Lung Cancer Patients: Correlation with Clinical Outcomes

OBJECTIVEnEpidermal growth factor receptor (EGFR) and K-ras mutations guide treatment selection in non-small cell lung cancer (NSCLC) patients. Although mutation status is routinely assessed in biopsies, cytological specimens are frequently the only samples available. We determined EGFR and K-ras mutations in cytological samples.nnnMETHODSnDNA was extracted from 150 consecutive samples, including 120 Papanicolau smears (80%), 10 cell blocks (7%), nine fresh samples (6%), six ThinPrep® tests (4%), and five body cavity fluids (3.3%). Papanicolau smears were analyzed when they had >50% malignant cells. Polymerase chain reaction and direct sequencing of exons 18-21 of EGFR and exon 2 of K-ras were performed. EGFR mutations were simultaneously determined in biopsies and cytological samples from 20 patients. Activity of EGFR tyrosine kinase inhibitors (TKIs) was assessed.nnnRESULTSnThe cytological diagnosis was adenocarcinoma in 110 samples (73%) and nonadenocarcinoma in 40 (27%) samples. EGFR mutations were identified in 26 samples (17%) and K-ras mutations were identified in 18 (12%) samples. EGFR and K-ras mutations were mutually exclusive. In EGFR-mutated cases, DNA was obtained from stained smears in 24 cases (92%), pleural fluid in one case (4%), and cell block in one case (4%). The response rate to EGFR TKIs in patients harboring mutations was 75%. The mutation status was identical in patients who had both biopsies and cytological samples analyzed.nnnCONCLUSIONnAssessment of EGFR and K-ras mutations in cytological samples is feasible and comparable with biopsy results, making individualized treatment selection possible for NSCLC patients from whom tumor biopsies are not available.

Erratum to: Role of [18F]FDG PET in prediction of KRAS and EGFR mutation status in patients with advanced non-small-cell lung cancer

PurposeThe tumour molecular profile predicts the activity of epidermal growth factor receptor (EGFR) inhibitors in non-small-cell lung cancer (NSCLC). However, tissue availability and tumour heterogeneity limit its assessment. We evaluated whether [18F]FDG PET might help predict KRAS and EFGR mutation status in NSCLC.MethodsBetween January 2005 and October 2011, 340 NSCLC patients were tested for KRAS and EGFR mutation status. We identified patients with stage III and IV disease who had undergone [18F]FDG PET/CT scanning for initial staging. SUVpeak, SUVmax and SUVmean of the single hottest tumour lesions were calculated, and their association with KRAS and EGFR mutation status was assessed. A receiver operator characteristic (ROC) curve analysis and a multivariate analysis (including SUVmean, gender, age and AJCC stage) were performed to identify the potential value of [18F]FDG PET/CT for predicting KRAS mutation.ResultsFrom 102 patients staged using [18F]FDG PET/CT, 28 (27xa0%) had KRAS mutation (KRAS+), 22 (22xa0%) had EGFR mutation (EGFR+) and 52 (51xa0%) had wild-type KRAS and EGFR profiles (WT). KRAS+ patients showed significantly higher [18F]FDG uptake than EGFR+ and WT patients (SUVmean 9.5, 5.7 and 6.6, respectively; pu2009<u20090.001). No significant differences were observed in [18F]FDG uptake between EGFR+ patients and WT patients. ROC curve analysis for KRAS mutation status discrimination yielded an area under the curve of 0.740 for SUVmean (pu2009<u20090.001). The multivariate analysis showed a sensitivity and specificity of 78.6xa0% and 62.2xa0%, respectively, and the AUC was 0.773.ConclusionNSCLC patients with tumours harbouring KRAS mutations showed significantly higher [18F]FDG uptake than WT patients, as assessed in terms of SUVpeak, SUVmax and SUVmean. A multivariate model based on age, gender, AJCC stage and SUVmean might be used as a predictive marker of KRAS mutation status in patients with stage III or IV NSCLC.

Assessment of EGFR and KRAS mutation status from FNAs and core-needle biopsies of non-small cell lung cancer

Molecular testing to determine gene mutation status is now the recommended standard of care for patients with advanced or metastatic Non‐small cell lung cancer (NSCLC). Because the majority of patients with NSCLC present with metastatic disease, minimally invasive procedures are necessary for diagnosis, staging, and molecular analysis. However, the resulting samples have perceived limitations in the oncology community, and most commercially available tests have not been validated for these sample types. The current study was undertaken to assess the feasibility of determining epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status in fine‐needle aspirates (FNAs) and core‐needle biopsies (CNBs) after staining with Papanicolaou or hematoxylin and eosin, respectively.

Variations in molecular profile in NSCLC can be analyzed using cytological samples: development of EGFR resistance mutations and coexistence of ALK-EML4 translocation in an EGFR-sensitive patient.

As a result of therapeutic advances, a revolution is taking place in the lung cancer field with major implications for pathologic diagnosis and tissue management. We report a case of a non–small cell lung carcinoma patient with coexistence of EGFR mutations and ALK-EML4 rearrangements that responded to EGFR inhibitors and in which the development of a new resistance mutation in exon 20 of EGFR-determined treatment resistance. All the molecular determinations were performed in cytological samples. To our knowledge, this is the first case reported with these characteristics, and the 11th case described with coexistence of EGFR mutations and ALK-EML4 rearrangements. The EGFR L858R mutation in exon 21 was found at diagnosis, and the patient presented a 4-year response to erlotinib. On progression, the T790M resistance mutation in the EGFR exon 20 was also confirmed in cytological samples. At this point, fluorescence in situ hybridization also detected ALK-EML4 translocation. This case emphasizes the usefulness of cytological samples for molecular analysis in lung adenocarcinoma, as well as the relevance of repeating biopsies/fine-needle aspirations in tumor recurrences to assess the mutation profile of the disease.

Hepatoblastoma en el adulto

Adult hepatoblastoma (AHB) is a very rare tumor, having been described 45 cases up to June 2012. In contrast to HB in infancy (IHB), it has poor prognosis. We present the case of a 37-year-old asymptomatic woman who consulted for a large –12 cm diameter– mass involving segments 5 and 6 of the liver, and alfa-fetoprotein of 1,556,30 UI/mL. A bisegmentectomy was carried out. The microscopic study confirmed the AHB diagnosis, revealing the presence of epithelial cells forming clusters, trabecular patterns and tubules. The patient died on the 10th postoperative month due to progression disease. The Wnt/β-Catenin signaling pathway mutation has been reported and associated with a poor prognosis in IHB. Due to the AHB poor prognosis, seems reasonable to introduce the therapeutic regimens described in children who have a better outcome.

Mechanical barriers and transforming growth factor beta inhibitor on epidural fibrosis in a rabbit laminectomy model

BackgroundTGF-β has been described as a mediator of fibrosis and scarring. Several studies achieved reduction in experimental scarring through the inhibition of TGF-β. Fibroblasts have been defined as the cell population originating fibrosis, blocking fibroblast invasion may impair epidural fibrosis appearance. For this purpose, biocompatible materials used as mechanical barriers and a TGF-β inhibitor peptide were evaluated in the reduction of epidural fibrosis.MethodsA L6 laminectomy was performed in 40 New Zealand white rabbits. Divided into four groups, each rabbit was assigned to receive either collagen sponge scaffold (CS group), gelatin-based gel (GCP group), P144® (iTGFβ group), or left untreated (control group). Four weeks after surgery, cell density, collagen content, and new bone formation of the scar area were determined by histomorphometry. Two experienced pathologists scored dura mater adhesion, scar density, and inflammatory infiltrate in a blinded manner.ResultsIn all groups, laminectomy site was filled with fibrous tissue and the dura mater presented adhesions. Only GCP group presented a significant reduction in collagen content and scar density.ConclusionGCP treatment reduces epidural fibrosis although did not prevent dura mater adhesion completely.

Gastroenteritis y colecistitis alitiásica en paciente varón de 34 años

Paciente varón de 34 años de edad, homosexual y sin antecedentes de interés que ingresa en nuestro hospital por un cuadro de gastroenteritis acompañado de febrícula y síndrome constitucional con pérdida de 20 kg de peso de 5 meses de evolución. No se habían aislado bacterias enteropatógenas en coprocultivos de rutina y tampoco se habían visualizado parásitos en heces. En la TAC abdominal (fig. 1) se evidenció un engrosamiento difuso de la pared de la vesícula biliar. No se objetivó colelitiasis ni barro biliar. La vía biliar (intray extrahepática) tenía un calibre normal. En la vecindad de la vesícula se observó un engrosamiento de 15 mm que afectaba a un segmento de 3,3 cm de la pared del antro gástrico que condicionaba una disminución del 90% del calibre de la luz. Se realizó una gastroscopia y se tomaron biopsias de la mucosa antral. Se recogió muestra de aspirado duodenal, que se envió a examen parasitológico (fig. 2). En la histopatología se observó un infiltrado inflamatorio de predominio plasmocitario. Además, se observó la presencia de numerosos microorganismos redondeados