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Japanese Journal of Clinical Oncology Advance Access published online on October 23, 2006
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hyl118
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© 2006 Foundation for Promotion of Cancer Research
Received May 15, 2006
Accepted August 18, 2006

Original Article

Telomere Length, Telomerase Activity, and Expressions of Human Telomerase mRNA Component (hTERC) and Human Telomerase Reverse Transcriptase (hTERT) mRNA in Pulmonary Neuroendocrine Tumors

Yuko Nishio 1, Kuniaki Nakanishi 2 *, Yuichi Ozeki 3, Shi-Xu Jiang 4, Toru Kameya 5, Akira Hebisawa 6, Makio Mukai 7, William D. Travis 8, Teri J Franks 9, and Toshiaki Kawai 1

1 Department of Pathology and Laboratory Medicine
2 Department of Pathology and Laboratory Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan
3 Department of Surgery, National Defense Medical College, Tokorozawa, Saitama
4 Department of Pathology, Kitasato University, Sagamihara, Kanagawa
5 Pathology Division, Shizuoka Cancer Center Hospital and Research Institute, Sunto-gun, Shizuoka
6 Department of Pathology, National Tokyo Hospital, Kiyose, Tokyo
7 Division of Diagnostic Pathology, Keio University School of Medicine, Tokyo, Japan
8 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
9 Armed Forces Institute of Pathology, Washington DC, USA

* To whom correspondence should be addressed.
Kuniaki Nakanishi, E-mail: nknsknak{at}ndmc.ac.jp


  Abstract

Background: Telomeres are important for chromosome structure and function, protecting them against degradation. However, few studies have examined telomeres in pulmonary neuroendocrine (NE) tumors.

Methods: We investigated deparaffinized sections obtained from 70 primary NE lung tumors [34 typical carcinoids (TCs), 10 atypical carcinoids (ACs), 16 large cell neuroendocrine carcinoma (LCNECs) and 10 small cell lung carcinomas (SCLCs)].

Results: Positive expressions of human telomerase mRNA component (hTERC) and human telomerase reverse transcriptase (hTERT) mRNA were recognized, respectively, in 58% and 74% of TCs, and in 100% and 100% of ACs, LCNECs and SCLCs. Alteration of telomere length was greater in both LCNECs and SCLCs than in TCs. Telomerase activity was detected in LCNECs, but not in TCs. By the reverse-transcriptase polymerase chain reaction (RT-PCR), hTERC mRNA was detected in 100% of LCNECs and TCs examined, while hTERT mRNA was detected in 67% of LCNECs, but not at all in TCs.

Conclusions: These results suggest that alterations in telomere length, telomerase activity, and the expression of hTERT mRNA may (i) play roles in pathogenesis in pulmonary neuroendocrine tumors, and (ii) be a useful tool for differential diagnosis between TCs and LCNECs.

Keywords: Telomere; telomerase; human telomerase mRNA component (hTERC); telomerase reverse transcriptase (hTERT); neuroendocrine tumors.
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