Classification of follicular-patterned thyroid lesions using a minimal set of epigenetic biomarkers

[Objective]: The minimally invasive fine-needle aspiration cytology (FNAC) is the current gold standard for the diagnosis of thyroid nodule malignancy. However, the correct discrimination of follicular neoplasia often requires more invasive diagnostic techniques. The lack of suitable immunohistochemical markers to distinguish between follicular thyroid carcinoma and other types of follicular-derived lesions complicates diagnosis, and despite most of these tumours being surgically resected, only a small number will test positive for malignancy. As such, the development of new orthogonal diagnostic approaches may improve the accuracy of diagnosing thyroid nodules.[Design]: This study includes a retrospective, multi-centre training cohort including 54 fresh-frozen follicular-patterned thyroid samples and two independent, multi-centre validation cohorts of 103 snap-frozen biopsies and 33 FNAC samples, respectively.[Methods]: We performed a genome-wide genetic and epigenetic profiling of 54 fresh-frozen follicular-patterned thyroid samples using exome sequencing and the Illumina Human DNA Methylation EPIC platform. An extensive validation was performed using the bisulfite pyrosequencing technique.[Results]: Using a random forest approach, we developed a three-CpG marker-based diagnostic model that was subsequently validated using bisulfite pyrosequencing experiments. According to the validation cohort, this cost-effective method discriminates between benign and malignant nodules with a sensitivity and specificity of 97 and 88%, respectively (positive predictive value (PPV): 0.85, negative predictive value (NPV): 0.98).[Conclusions]: Our classification system based on a minimal set of epigenetic biomarkers can complement the potential of the diagnostic techniques currently available and would prioritize a considerable number of surgical interventions that are often performed due to uncertain cytology.[Significance statement]: In recent years, there has been a significant increase in the number of people diagnosed with thyroid nodules. The current challenge is their etiological diagnosis to discount malignancy without resorting to thyroidectomy. The method proposed here, based on DNA pyrosequencing assays, has high sensitivity (0.97) and specificity (0.88) for the identification of malignant thyroid nodules. This simple and cost-effective approach can complement expert pathologist evaluation to prioritize the classification of difficult-to-diagnose follicular-patterned thyroid lesions and track tumor evolution, including real-time monitoring of treatment efficacy, thereby stimulating adherence to health promotion programs.Peer reviewe

Çédille, revista de estudios franceses

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El pasado mes de abril iniciamos una nueva etapa en Çédille, representada principalmente por su traslado a la plataforma Open Journal System (OJS) de la Universidad de La Laguna, así como por la renovación y reasignación de competencias del Consejo de Redacción. Durante este tiempo, hemos tenido que adaptarnos, experimentar y comprender, pacientemente, el funcionamiento de esta nueva herramienta que es OJS. Ello ha supuesto, en algunos casos, que se hayan producido determinadas dificultades de comunicación con nuestros lectores y evaluadores, o que se hayan ocasionado pequeños retrasos en la gestión de la revista. Como nuestros seguidores saben, muy recientemente hemos sufrido, además, un ataque informático que no solo impidió el acceso a la plataforma durante varios días (justo en el momento final de producción de este número), sino que obligó a trasladar nuestro sitio web a otro servidor y a implementar nuevas medidas de seguridad. Afortunadamente, gracias al buen hacer y profesionalidad de Juan Ascanio Amigó, asesor técnico de OJS para la Universidad de La Laguna, hemos logrado salir airosos de los problemas, complicaciones y secuelas que nos hemos ido encontrando en este tiempo. En este número que ahora ve la luz contamos con treinta y cuatro contri-buciones que superan, en total, las setecientas páginas. Así, Amelia Gamoneda Lanza y Francisco González Fernández se han encargado de coordinar una nueva entrega –la undécima– de la serie «Monografías», donde han reunido una ..