Thyroid follicular adenomas and carcinomas: molecular profiling provides evidence for a continuous evolution

// Geneviève Dom 1 , Sandra Frank 1 , Sebastien Floor 1 , Pashalina Kehagias 1 , Frederick Libert 1 , Catherine Hoang 3 , Guy Andry 4 , Alex Spinette 4 , Ligia Craciun 4 , Nicolas de Saint Aubin 4 , Christophe Tresallet 3 , Frederique Tissier 3 , Frederique Savagner 5 , Samira Majjaj 4 , Ilse Gutierrez-Roelens 6 , Etienne Marbaix 6 , Jacques E. Dumont 1 and Carine Maenhaut 1, 2 1 Institute of Interdisciplinary Research (IRIBHM), Université libre de Bruxelles (ULB), Brussels, Belgium 2 WELBIO, School of Medicine, Université libre de Bruxelles, Brussels, Belgium 3 Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris, France 4 Institut Jules Bordet, Brussels, Belgium 5 IFB, Hôpital Toulouse Purpan, Toulouse, France 6 Biolibrary of the King Albert II Institute, Cliniques Universitaires Saint-Luc, and Institut de Duve, Université Catholique de Louvain, Brussels, Belgium Correspondence to: Geneviève Dom, email: genedom@ulb.ac.be Keywords: thyroid follicular carcinoma; thyroid follicular adenoma; malignant progression mRNA; miRNA Received: October 19, 2016 Accepted: November 14, 2017 Published: December 08, 2017 ABSTRACT Non-autonomous thyroid nodules are common in the general population with a proportion found to be cancerous. A current challenge in the field is to be able to distinguish benign adenoma (FA) from preoperatively malignant thyroid follicular carcinoma (FTC), which are very similar both histologically and genetically. One controversial issue, which is currently not understood, is whether both tumor types represent different molecular entities or rather a biological continuum. To gain a better insight into FA and FTC tumorigenesis, we defined their molecular profiles by mRNA and miRNA microarray. Expression data were analyzed, validated by qRT-PCR and compared with previously published data sets. The majority of deregulated mRNAs were common between FA and FTC and were downregulated, however FTC showed additional deregulated mRNA. Both types of tumors share deregulated pathways, molecular functions and biological processes. The additional deregulations in FTC include the lipid transport process that may be involved in tumor progression. The strongest candidate genes which may be able to discriminate follicular adenomas and carcinomas, CRABP1, FABP4 and HMGA2, were validated in independent samples by qRT-PCR and immunohistochemistry. However, they were not able to adequately classify FA or FTC, supporting the notion of continuous evolving tumors, whereby FA and FTC appear to show quantitative rather than qualitative changes. Conversely, miRNA expression profiles showed few dysregulations in FTC, and even fewer in FA, suggesting that miRNA play a minor, if any, role in tumor progression.