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Journal Article 2011; 32(1): 59-63 PubMed PMID: 21407159 Citation  Keywords:  Biopsy, Fine-Needle, Carcinoma, Female, Gene Expression Regulation, Neoplastic, Humans, Male, Neoplasm Staging, Phosphatidylinositol 3-Kinases:genetics, RNA, Messenger:metabolism, Thyroid Neoplasms:genetics,.   

INTRODUCTION: Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland. The pathogenesis of PTC remains still mostly enigmatic, although PI3K/PTEN/AKT pathway has been proposed to play a role in development of PTC. Moreover, the significance of genetic analysis in the material from fine-needle aspiration biopsy (FNAB) in PTC patients has recently been demonstrated. Hereby, we present a study analyzing expression of PIK3CA in FNAB washouts of PTC and a comparison of the level of that expression with respective expression in postoperative PTC tissue. Furthermore, we have assessed correlation between tumor size, evaluated according to pTNM scale, and level of PIK3CA gene expression in postoperative PTC tissue.

METHODS: Total RNA was extracted by use of an RNeasy Micro Kit (Qiagen, Hilden, Germany) in FNAB material, and RNeasy Midi Kit (Qiagen, Hilden, Germany) in tissue material. The purity of total RNA was assessed by NanoDrop® ND-100 spectrophotometr. One hundred nanograms of total RNA were used in the first strand cDNA synthesis with TaqMan® Reverse Transcripton Reagents (Applied Biosystems, Branchburg, New Jersey, USA). The gene expression level of PIK3CA was analyzed by real-time PCR in the ABI PRISM ®7500 Sequence Detection System in the 21 (17 women, 4 men) FNAB and 20 (16 women, 4 men) postsurgical specimens of PTC. pTNM staging of PTC was assessed based on UICC classification.

RESULTS: Overexpression of PIK3CA was confirmed in FNAB washout specimens and in postoperative tissues of PTC, in comparison to macroscopically unchanged thyroid tissue. Furthermore, statistically significant differences in PIK3CA gene expression levels between both examined groups were not confirmed. Moreover, correlation between pTNM staging and level of PIK3CA gene expression in PTC samples was not found.

CONCLUSION: The genetic analysis of overexpression of PIK3CA in FNAB washout specimens may be equivalent of postsurgical PTC tissue. A possibility of its future clinical application in FNAB specimens - adequate or undetermined for cytological analysis - awaits for evaluation. The level of expression of PIK3CA is independent of primary thyroid tumour size, evaluated according pTNM scale....

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Journal Article 2007; 28(3): 221-229 PubMed PMID: 17627253 Citation  Keywords:  Carcinoma, Papillary:genetics, Gene Rearrangement, Genotype, Humans, Neoplasms, Radiation-Induced:genetics, Phenotype, Proto-Oncogenes, Receptor, trkA:genetics, Thyroid Neoplasms:genetics,.   

: Papillary thyroid carcinoma (PTC) represents an example of tumour with high incidence of oncogenic sequences, such as RET/PTC and Trk. Both of them arise from the fusion of 3' terminal sequences of TK domain of RET or NTRK1 gene, respectively, with 5' terminal sequences of their activating genes. In case of NTRK1 oncogene, several rearrangement types are observed, characteristic for PTC: Trk (TMP3), Trk-T1, Trk-T2, Trk-T3 and Trk-2h, observed in human breast cancer cell line. Studies from different geographical regions, revealed significant population differences in the incidence of Trk rearrangements (0-50%), while within the same population, the frequency of Trk in spontaneous and radiation-associated PTCs is similar. The results of studies, focused on the correlation between tumour genotype and the histopathological type of tumour, involving cases of both RET/PTC and Trk rearrangements in PTC, are not unequivocal. In many studies, no correlation was observed between the presence of RET and/or NTRK1 rearrangement and such parameters, as patient's age at diagnosis, gender, histopathological type of tumour or clinical stage (TNM stage grouping), although the earliest clinical symptoms and the worst disease outcomes were observed for RET/NTRK1 rearrangement positive tumours. Differences in the rearrangement incidence between male and female patients were associated with the latency period of radiation-associated tumours, being significantly lower in women. In general, it is assumed that oncogenic Trk sequences are typical for the spontaneous type of PTC....

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