Clinical, pathological and genetic features of anaplastic and poorly differentiated thyroid cancer: A single institute experience

Abstract

Anaplastic (ATC) and poorly differentiated thyroid cancer (PDTC) are very aggressive cancers whose histological diagnosis is not always straightforward. Clinical, pathological and genetic features may be useful to improve the identification of these rare histotypes. In the present study the clinical, pathological and genetic features of two groups of ATC (n=21) and PDTC (n=21) patients were analyzed. Clinical data were retrieved from a computerized database. The oncogenic profiles were studied using the Sanger sequencing method of a selected series of oncogenes and/or tumor suppressor genes known to be altered in these tumors. The presence of macrophages in both series of tissues was evaluated by immunohistochemistry. Patients with ATC were older and affected by a more advanced disease at diagnosis than those with PDTC. The median survival was significantly shorter in ATC compared with PDTC patients (P=0.0014). ATC showed a higher prevalence of <i>TP53</i> and <i>TERT</i> mutations (10/21, 47.6% and 9/21, 42.8%, respectively) while <i>TERT</i> and <i>BRAF</i> mutations were the most prevalent in the PDTC group (7/21, 33.3% and 4/23, 19% respectively). Genetic heterogeneity (i.e., >2 mutations) was more frequent in ATC (10/21, 28.6%) compared with in PDTC (3/21, 4.7%) (P=0.03). Macrophages were more frequently present in ATC, particularly in those cases with <i>TP53</i> mutations. In conclusion, these data indicate that ATC and PDTC may be characterized by different clinical, pathological and genetic profiles. In particular ATC, but not PDTC, were positive for <i>TP53</i> and <i>PTEN</i> alterations. Complex mutations were also found in ATC but not in PDTC. Moreover, genetic heterogeneity was more frequent in ATC than PDTC. Finally, <i>TP53</i> mutation and the accumulation of several mutations correlated with a shorter survival time.