Pulmonary large cell neuroendocrine carcinoma demonstrates high proliferative activity.
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 1000 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.
Iyoda
Akira
A
Department of Thoracic Surgery, Chiba, Japan.
Hiroshima
Kenzo
K
Moriya
Yasumitsu
Y
Mizobuchi
Teruaki
T
Otsuji
Mizuto
M
Sekine
Yasuo
Y
Shibuya
Kiyoshi
K
Iizasa
Toshihiko
T
Saitoh
Yukio
Y
Fujisawa
Takehiko
T
D000328:Adult; D000368:Aged; D018287:Carcinoma, Large Cell / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D018278:Carcinoma, Neuroendocrine / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D002455:Cell Division; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008175:Lung Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53