Molecular Alterations in Relation to Histopathological Characteristics in a Large Series of Pediatric Papillary Thyroid Carcinoma from a Single Institution

• Main Authors: Elisabetta Macerola, Agnese Proietti, Anello Marcello Poma, Clara Ugolini, Liborio Torregrossa, Paola Vignali, Alessio Basolo, Gabriele Materazzi, Rossella Elisei, Ferruccio Santini, Fulvio Basolo
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: Cancers
• Subjects: papillary thyroid carcinoma; pediatric thyroid cancer; molecular pathology; gene mutation; gene fusion
• Online Access: https://www.mdpi.com/2072-6694/13/13/3123

Papillary thyroid carcinoma (PTC) presents distinct clinico-pathological and molecular differences in children compared with adult patients. Whether the presence of rearrangements or point mutations is associated with aggressive PTC clinical presentation is still controversial. In this study, PTCs diagnosed in patients aged less than 18 years were retrospectively searched from the institutional archive and tumor tissue was tested for point mutations in <i>BRAF</i> and <i>RAS</i> genes and for rearrangements in <i>RET</i>, <i>NTRK1</i>, <i>NTRK3</i>, <i>ALK</i>, <i>PPARG</i>, <i>BRAF</i> and <i>THADA</i>. A total of 163 PTCs were analyzed. Point mutations were found in 83 (51%) and gene fusions in 48 cases (30%). The most frequent alteration was the <i>BRAF</i>^V600E mutation (36.8%), followed by <i>NTRK3</i> fusion (11%), <i>NRAS</i> mutation (10.4%) and <i>RET</i> fusion (10.4%). Fusion-driven PTCs showed more frequently infiltrative growth, larger tumors, extrathyroidal extension and N1b disease. PTCs showing solid growth pattern were significantly enriched in gene fusions. This is one of the largest cohorts of pediatric PTCs. Fusion-driven tumors most frequently show aggressive pathological features; the search for rearrangements, especially in tumors with solid areas, could improve the characterization of pediatric PTCs and offer possible therapeutic options.