Amplification of the human epidermal growth factor receptor 2 gene in differentiated thyroid cancer correlates with telomere shortening

Sugishita,Yoshiyuki; Kammori,Makoto; Yamada,Osamu; Poon,Steven  S.S.; Kobayashi,Makio; Onoda,Naoyoshi; Yamazaki,Kazuko; Fukumori,Tatsuya; Yoshikawa,Kei-Ichi; Onose,Hiroyuki; Ishii,Shinnya; Yamada,Emiko; Yamada,Tetsu

doi:10.3892/ijo.2013.1848

Amplification of the human epidermal growth factor receptor 2 gene in differentiated thyroid cancer correlates with telomere shortening

Authors:
- Yoshiyuki Sugishita
- Makoto Kammori
- Osamu Yamada
- Steven S.S. Poon
- Makio Kobayashi
- Naoyoshi Onoda
- Kazuko Yamazaki
- Tatsuya Fukumori
- Kei-Ichi Yoshikawa
- Hiroyuki Onose
- Shinnya Ishii
- Emiko Yamada
- Tetsu Yamada
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Affiliations: Department of Clinical Pathology, Kanaji Hospital, Kita-ku, Tokyo 114-0015, Japan, Department of Surgery, Kanaji Hospital, Kita-ku, Tokyo 114-0015, Japan, Medical Research Institute, Tokyo Women's Medical University, Shinjuku-ku, Tokyo 162-8666, Japan, Terry Fox Laboratory, British Columbia Cancer Research Center, Vancouver, BC V5Z1L3, Canada, Department of Clinical Pathology, Mithuwadai General Hospital, Wakaba-ku, Chiba 264-0021, Japan, Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan, Department of Internal Medicine, Kanaji Hospital, Kita-ku, Tokyo 114-0015, Japan
Published online on: March 5, 2013 https://doi.org/10.3892/ijo.2013.1848
Pages: 1589-1596

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Abstract

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.

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