Tohoku J. Exp. Med., 2007, 213(1)

Ets-1 Proto-Oncogene as a Potential Predictor for Poor Prognosis of Lung Adenocarcinoma

EIICHIRO YAMAGUCHI,¹ TOSHIYUKI NAKAYAMA,² ATSUSHI NANASHIMA,¹ KEITARO MATSUMOTO,¹ TORU YASUTAKE,¹ ICHIRO SEKINE² and TAKESHI NAGAYASU¹

¹Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
²Division of Tumor and Diagnostic Pathology, Atomic Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

The proto-oncogene Ets-1 is a transcription factor that is known to regulate certain matrix metalloproteinases and plasminogen activator, which have been associated with malignant behaviors in solid carcinomas. We hypothesized that Ets-1 expression is also associated with tumor progression and a worse prognosis in lung carcinoma patients. To clarify the role of the Ets-1 proto-oncogene, the expression of Ets-1 in non-small cell lung carcinomas using 156 paraffin-embedded specimens was determined in surgically resected tissue samples. Immunohistochemical staining showed Ets-1 expression in 82 cases of 156 carcinomas (53%): 36 of 52 (69%) squamous cell carcinomas, 41 of 96 (43%) adenocarcinomas, and 5 of 8 (63%) other carcinomas. In adenocarcinomas, a higher proportion of acinar type expressed Ets-1 compared to papillary or alveolar type (p < 0.05). The proportion of adenocarcinoma that expressed Ets-1 increased with poorer histologic differentiation of the adenocarcinoma (p < 0.05). Ets-1 positive adenocarcinomas had a larger mean size than Ets-1 negative adenocarcinomas (p < 0.01). In adenocarcinoma patients, expression of Ets-1 was associated with disease-free (p = 0.09) and overall survivals (p < 0.05) after lung resection. Such relationship was not observed among squamous cell carcinoma patients. Our findings indicate that Ets-1 expression is related to histopathological differentiation, morphogenesis, and tumor progression of lung adenocarcinomas. Ets-1 appears to be a useful predictor of poor prognosis after surgical resection in lung adenocarcinoma patients. Ets-1 expression could be used to evaluate the malignant behaviors of lung adenocarcinomas.

keywords —— Ets-1; non-small cell lung cancer; histologic differentiation; subtype; prognosis

© 2007 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2007, 213, 41-50

Correspondence: Takeshi Nagayasu, Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.

e-mail: nagayasu@net.nagsaki-u.ac.jp