Amplification of the human epidermal growth factor receptor 2 gene in differentiated thyroid cancer correlates with telomere shortening
| Autor: | Shinnya Ishii, Hiroyuki Onose, Steven S.S. Poon, Makio Kobayashi, Naoyoshi Onoda, Osamu Yamada, Makoto Kammori, Yoshiyuki Sugishita, Kei-ichi Yoshikawa, Tatsuya Fukumori, Emiko Yamada, Tetsu Yamada, Kazuko Yamazaki |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Cancer Research Telomerase Receptor ErbB-2 Biology Antibodies Monoclonal Humanized Proto-Oncogene Mas Breast cancer Trastuzumab medicine Humans Telomerase reverse transcriptase Thyroid Neoplasms skin and connective tissue diseases neoplasms Thyroid cancer In Situ Hybridization Fluorescence Telomere Shortening Aged medicine.diagnostic_test Thyroid Gene Amplification Cancer Cell Differentiation Middle Aged medicine.disease Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology Cancer research Female Fluorescence in situ hybridization medicine.drug |
| Zdroj: | International Journal of Oncology. 42:1589-1596 |
| ISSN: | 1791-2423 1019-6439 |
| DOI: | 10.3892/ijo.2013.1848 |
| Popis: | The human epidermal growth factor receptor 2 (HER2) proto-oncogene plays an important role in the development and progression of breast and gastric cancer. Monitoring of the HER2 status and treatment with trastuzumab was performed initially in breast cancer, and subsequently in gastric cancer. However, the HER2 status of thyroid cancer remains unexplored. Telomere alteration and telomerase activity have been observed in most human cancers and are known to be a feature of malignancy. The aims of this study were to clarify the HER2 status of thyroid cancer and to examine any correlations to various characteristics of malignancy. We investigated 69 cases of differentiated thyroid cancers with reference to: i) telomere length as measured using tissue quantitative fluorescence in situ hybridization (Q-FISH), ii) expression of human telomerase reverse transcriptase (hTERT) as determined by immunohistochemistry (IHC), and iii) overexpression of the HER2 protein as determined by IHC and amplification of the HER2 gene as determined by fluorescence in situ hybridization (FISH). The telomeres of thyroid cancers, especially follicular carcinomas, were significantly shorter compared to those of adjacent normal tissues. Positivity for hTERT expression and HER2 amplification were observed in approximately 70 and 22% of thyroid cancers, respectively. Our data demonstrated that telomeres in HER2-positive cancers were significantly shorter compared to those in HER2-negative cancers. These results suggest that highly malignant differentiated thyroid cancer can be detected by monitoring HER2 status and telomere shortening, and that trastuzumab therapy may be effective for refractory thyroid cancer. |
| Databáze: | OpenAIRE |
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