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Ann Thorac Surg 2004;77:1891-1895
© 2004 The Society of Thoracic Surgeons

Original article: general thoracic

Pulmonary large cell neuroendocrine carcinoma demonstrates high proliferative activity

Akira Iyoda, MDa, Kenzo Hiroshima, MDb, Yasumitsu Moriya, MDa, Teruaki Mizobuchi, MDa, Mizuto Otsuji, MDa, Yasuo Sekine, MDa, Kiyoshi Shibuya, MDa, Toshihiko Iizasa, MDa, Yukio Saitoh, MDa, Takehiko Fujisawa, MDa*

a Department of Thoracic Surgery, Chiba, Japan
b Department of Basic Pathology, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan

Accepted for publication October 28, 2003.

* Address reprint requests to Dr Fujisawa, Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan
e-mail: fujisawa{at}med.m.chiba-u.ac.jp

BACKGROUND: In 1999, the World Health Organization classified large cell neuroendocrine carcinoma as a variant of large cell carcinoma and this has been categorized as lying between atypical carcinoid and small cell lung carcinoma in terms of clinical aggressiveness.

METHODS: We analyzed the proliferative activity of stage 1 large cell neuroendocrine carcinoma derived from patients with primary lung cancer who underwent surgical resection and compared the results with stage 1 classic large cell carcinoma cases. The mitotic rate was counted in ten high-power fields of light microscope. Immunohistochemical staining using anti-Ki-67 antibody was performed. The Ki-67 labeling index, expressed as a percentage of positive cells, was determined by light microscopy with random counting of at least 1,000 tumor nuclei. The expression of P53 and Bcl-2 was examined and compared.

RESULTS: The mitotic rate of large cell neuroendocrine carcinoma cases was significantly higher than that of classic large cell carcinoma cases. The Ki-67 labeling index of stage 1 large cell neuroendocrine carcinoma cases was significantly higher than that of stage 1 classic large cell carcinoma cases. Immunohistochemical expression of P53 in large cell neuroendocrine carcinoma and classic large cell carcinoma was comparable. However, large cell neuroendocrine carcinoma exhibited a significantly higher expression of Bcl-2 than classic large cell carcinoma. The disease specific disease-free survival for patients with stage 1 large cell neuroendocrine carcinoma was significantly lower than that for patients with stage 1 classic large cell carcinoma.

CONCLUSIONS: Large cell neuroendocrine carcinoma appears to be more clinically aggressive than classic large cell carcinoma with these findings indicating that large cell neuroendocrine carcinoma has a higher level of proliferative activity than classic large cell carcinoma.




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