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

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  • Yamaguchi Eiichiro
    Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences
  • Nakayama Toshiyuki
    Division of Tumor and Diagnostic Pathology, Atomic Disease Institute, Nagasaki University Graduate School of Biomedical Sciences
  • Nanashima Atsushi
    Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences
  • Matsumoto Keitaro
    Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences
  • Yasutake Toru
    Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences
  • Sekine Ichiro
    Division of Tumor and Diagnostic Pathology, Atomic Disease Institute, Nagasaki University Graduate School of Biomedical Sciences
  • Nagayasu Takeshi
    Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences

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Abstract

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.

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