1. ¹Department of Pathology, Experimental Molecular Pathology, Istituto Nazionale Tumori, Milan, Italy
2. ²Department of Experimental Oncology, Operative Unit 'Molecular Mechanisms of Cancer Growth and Progression', Istituto Nazionale Tumori, Via G Venezian, 1, Milan 20133, Italy
3. ³IFOM Foundation (The Firc Institute for Molecular Oncology Foundation), Milan, Italy

Correspondence: MA Pierotti or A Greco, Istituto Nazionale Tumori, Department of Experimental Oncology Operative Unit 'Molecular Mechanisms of Cancer Growth and Progression', Via G Venezian, 1 20133 Milan Italy. E-mail: marco.pierotti@istitutotumori.mi.it or angela.greco@istitutotumori.mi.it

Received 8 March 2004; Revised 17 June 2004; Accepted 22 June 2004; Published online 26 July 2004.

Abstract

Papillary thyroid carcinoma (PTC) is associated with RET and NTRK1 rearrangements and BRAF mutations. A series of 60 PTCs collected in a single center from Italian patients were histologically re-examined and subclassified as well differentiated or tall cell variant. The sample collection was analysed for the presence of all the reported PTC-associated genetic alterations through DNA or cDNA amplification, followed by automated sequencing. The analysis of exons 11 and 15 of BRAF gene revealed the T1796A (V599E) mutation in 32% of cases, and this alteration is significantly associated with PTC tall cell variant. Oncogenic rearrangements of RET and NTRK1 receptors were found in 33 and 5% of cases, respectively. No Ras mutations were detected. Overall, genetic alterations were detected in two-thirds of samples, and in no single case more than one mutational event was found simultaneously. Gene expression profiling of a subset of 31 tumors performed using cDNA microarray chips showed no strong differences in global gene expression among the different cases. However, a supervised analysis of the obtained data identified a subset of genes differentially expressed in tumors carrying BRAF mutation or RTK rearrangement.