The Tumor-Specific Expression of L1 Retrotransposons Independently Correlates with Time to Relapse in Hormone-Negative Breast Cancer Patients

Background: Long-Interspersed Nuclear Element (L1) retrotransposons are silenced in healthy tissues but unrepressed in cancer. Even if L1 reactivation has been associated with reduced overall survival in breast cancer (BC) patients, a comprehensive correlation with clinicopathological features is still missing. Methods: Using quantitative, reverse-transcription PCR, we assessed L1 mRNA expression in 12 BC cells, 210 BC patients and in 47 normal mammary tissues. L1 expression was then correlated with molecular and clinicopathological data. Results: We identified a tumor-exclusive expression of L1s, absent in normal mammary cells and tissues. A positive correlation between L1 expression and tumor dedifferentiation, lymph-node involvement and increased immune infiltration was detected. Molecular subtyping highlighted an enrichment of L1s in basal-like cells and cancers. By exploring disease-free survival, we identified L1 overexpression as an independent biomarker for patients with a high risk of recurrence in hormone-receptor-negative BCs. Conclusions: Overall, L1 reactivation identified BCs with aggressive features and patients with a worse clinical fate

Pursuit of Gene Fusions in Daily Practice: Evidence from Real-World Data in Wild-Type and Microsatellite Instable Patients

Agnostic biomarkers such as gene fusions allow to address cancer patients to targeted therapies; however, the low prevalence of these alterations across common malignancies poses challenges and needs a feasible and sensitive diagnostic process. RNA-based targeted next generation sequencing was performed on 125 samples of patients affected either by colorectal carcinoma, melanoma, or lung adenocarcinoma lacking genetic alterations in canonical driver genes, or by a colorectal carcinoma with microsatellite instability. Gene fusion rates were compared with in silico data from MSKCC datasets. For NTRK gene fusion detection we also employed a multitarget qRT-PCR and pan-TRK immunohistochemistry. Gene fusions were detected in 7/55 microsatellite instable colorectal carcinomas (12.73%), and in 4/70 of the “gene driver free” population (5.71%: 3/28 melanomas, 10.7%, and 1/12 lung adenocarcinomas, 8.3%). Fusion rates were significantly higher compared with the microsatellite stable and “gene driver positive” MSKCC cohorts. Pan-TRK immunohistochemistry showed 100% sensitivity, 91.7% specificity, and the occurrence of heterogeneous and/or subtle staining patterns. The enrichment of gene fusions in this “real-world” cohort highlights the feasibility of a workflow applicable in clinical practice. The heterogeneous expression in NTRK fusion positive tumours unveils challenging patterns to recognize and raises questions on the effective translation of the chimeric protein

Coping with formalin banning in pathology: under vacuum long-term tissue storage with no added formalin

Formalin is toxic and has recently been classified as carcinogenic leading to a proposed European formalin ban. But, the pathology use of formalin has however been completely overlooked, and this is proving to be a relevant issue, as no alternative, reliable, tissue fixative is available. Various systems have been proposed to reduce formalin use and exposure; long-term storage and disposal of formalin is also a problem. With this in mind, under vacuum sealing (UVS) systems have been proposed for transportation/storage, however, for how long tissue retains its characteristics (morphological and molecular) is unknown. This study aims to compare histology specimens stored by formalin immersion (FI) and specimens stored after fixation with UVS technique with no additional formalin, at different time periods. Twenty tissue samples (10FI; 10UVS) were stored for different time periods (15 days, 1\u20132\u20133\u20136\u201312 months) for a total of 120 samples, compared with regard to their morphology, histochemistry, immunoreactivity (24 specific antibodies) and DNA status. All samples showed well-preserved morphology and overlapping staining quality. A significant reduction in immunoreactivity was however identified in the various time periods, particularly for heat pre-treated nuclear antigens, and this commenced earlier (1 month) for FI. UVS storage showed higher DNA content than FI but slightly poorer DNA integrity. These results add important knowledge to the use of UVS in daily practice, as long-term storage of pre-fixed tissue in UVS is not detrimental to the quality of tissue while having the boon of using very little formalin with less operator exposure and lower disposal costs

Typo EINA 15 years

Aquest llibre commemora els 15 anys dels cursos de tipografia a Eina. Han estat 15 edicions de durades i continguts diferents però que sempre han considerat la lletra com la manera per entendre i construir la pàgina. Les primeres tres edicions no van tenir cap mena de tiulació per després passar a un postgrau i finalment a un màster de títol propi de la Universitat Autònoma de Barcelona. A les pàgines següents, trobareu les dates, la llista de professors i la llista d’alumnes de cada curs i, a continuació, una tria de treballs destacats d’alguns alumnes que han cursat els estudis. En fer aquesta publicació, un cop acabada la tria, és quan ens hem adonat de la importància d’allò que ha deixat el curs i de com de diferents són els ambits relacionats amb la lletra.Este libro conmemora los 15 años de los cursos de tipografía en Eina. Han sido 15 ediciones de duraciones y contenidos diferentes pero que siempre han considerado la letra como la forma de entender y construir la página. Las primeras tres ediciones no tuvieron forma de titulación alguna, para después pasar a un posgrado y finalmente a un máster de título propio en la Universitat Autònoma de Barcelona. Encontraréis en la siguientes páginas las fechas, la lista de profesores y la lista de alumnos de cada curso, y a continuación una selección de trabajos destacados de quienes pasaron por los cursos. Al hacer esta publicación, una vez terminada la selección, es cuando nos hemos dado cuenta de cómo de importante es lo que ha dejado el curso y de cómo de diferentes son los ámbitos relacionados con la letra.This book commemorates 15 years of typography courses at Eina. These courses have had different lengths and contents, but all have considered the letter as the key to understanding and building the page. For the first three years, there was no formal degree attached to the program, but Typography later became a postgraduate degree and finally an accredited Master´s degree from Autonomous University of Barcelona. In the following pages you’ll find the dates, professors and students of each year of the program, followed by a selection of outstanding projects. Putting this publication together was a reminder of just how important this course is, and of the many different ways there are of thinking about letters