Endocrine Abstracts (2009) 20 P63

Analysis of the genetic markers: ANLN, BIRC5, UBE2C, IRAK1, ZMYCD11, CENPA in needle aspiration cytology (FNA) of thyroid and their used as targets for molecular-diagnosis and prognostic value

Eugenia Mato1, Jesús Martín-Campos2, Josefina Mora3, Enrique Lerma4, Olga Bell1 & Alberto de Leiva1,5

1Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Hospital Santa Creu i Sant Pau, Autonomous University, Barcelona, Spain; 2Department of Biochemistry and Molecular Biology, Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Autonomous University, Barcelona, Spain; 3Department of Clinical Biochemistry, Hospital Santa Creu i Sant Pau, Autonomous University, Barcelona, Spain; 4Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University, Barcelona, Spain; 5Endocrinology Department, Hospital Sant Pau, Autonomous University, Barcelona, Spain.

Thyroid carcinoma is the most common endocrine malignancy. However, the absence of prognostic markers for identified well-differentiated tumors versus undifferentiated/anaplastic or poorly differentiated enhances of the progression of recurrent forms with an unfavorable prognosis. In order to identify potential markers for thyroid cancer prognosis prediction, we analyzed by cDNA micro-array the gene expression profile of tumors of the thyroid, with different degrees of malignancy, allowed identifying 23 genes can predicted a worse prognosis in the patients. Fine needle aspiration cytology (FNAC) is a well-established technique for pre-operative investigation of thyroid nodule(s). This technique is an efficient method of differentiating benign versus malignant thyroid nodules; however, the molecular techniques are not routinely applied in FNAC and their implement can be used for improved more efficiency the diagnosis.

Aim: The purpose of this study was to evaluate if the molecular analysis using residual samples of FNAC, is feasible and could be employed for molecular preoperative studies in the future. Moreover, if the expression of genes considered like as specific molecular signature, are useful as a target for molecular-diagnosis routine using FNAC.

Methods: The expression of ANLN, BIRC5, UBE2C, IRAK1, ZMYND11, CENPA mRNA in 22 thyroid benign tumors and 24 papillar carcinoma (PTC) and 5 normal thyroid tissues by means of the cDNA analysis through the qRT-PCR technology in the Abi7000 platform. The relative expression levels were determined by Comparative CT Method using normal thyroid samples as a tissue calibration control expression.

Results: RNA was successfully isolated in 50% (11/22) of thyroid benign tumors tested, and 79.1% (19/24) in PTC. The expression of the genes: ANLN, ZMYND-11, IRAK-1 from PTC, showed an increase of the 3.4-fold, 21.7-fold and 963.5-fold mRNA levels respectively compared to the control tissue with statistically significant. Moreover, in samples from benign tumors their increase expressions were lower: 2.9-fold (ANLN), 8.9-fold (ZMYND-11) and 468.7-fold (RAK-1), when the results were compared with the PTC. The analyses of the genes UBE2C, BIRC5 and CENPA, showed also a significally increase in FNAC from PTC samples, 118.2-fold, 16.3-fold and 63.1-fold respectively compared with the control. However, they were lower when we compare these results with the benign tumors: 591.2-fold (UBE2C), 56.5-fold (BIRC5) and 319.9-fold (CENPA).

Summary: FNAC can be used to evaluate gene expression by qRT-PCR technology, without modifying the routine procedure. The expression of the genes ANLN, ZMYND-11, IRAK-1 can be useful in the suspicious samples. However, the expression of the genes UBE2C, BIRC5 AND CENPA increases cannot useful to differentiate between benign hyperplasia versus PTC. Finally, these results suggest the usefulness of the quantitative measurement of ANLN, ZMYND-11, IRAK1 mRNA in molecular-based diagnosis of thyroid PTC. Further analysis with undifferentiated/anaplastic or poorly differentiated tumors would be of interest.

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