Discrimination of Multiple Primary Lung Cancers From Intrapulmonary Metastasis Based on the Expression of Four Cancer-related Proteins

BACKGROUND: Because distinguishing between multiple primary lung cancers and intrapulmonary metastasis is often difficult when the tumor histology is same, the feasibility of analyzing differential protein expression profiles to distinguish multiple primary lung cancers from intrapulmonary metastasis was evaluated. METHODS: This study enrolled 50 patients, with multiple primary lung cancers demonstrating the same histology, who underwent surgery between April 1994 and March 2006 and 20 patients who were diagnosed to have intrapulmonary metastasis during the same period. Thirty patients with lymph-node metastasis were selected for comparison purposes. The sum value of the differences in the expression ratio of 4 proteins (p53, p16, p27, and c-erbB2) was evaluated in immunohistochemically stained specimens among multiple primary lung cancers and intrapulmonary metastasis. RESULTS: None of the 30 patients with lymph-node metastasis showed a sum value of the differences between primary tumor and lymph-node metastasis in the 4 protein expression ratios >90. Therefore, when the difference between 2 tumors exceeded 90, the 2 tumors were considered to be different from each other, ie, multiple primary lung cancers. Forty-one of 50 (82%) patients who were clinically diagnosed to have multiple primary lung cancers showed a sum value of the differences in their protein expression ratios >90, 4 of 20 (20%) patients who were clinically diagnosed to have intrapulmonary metastasis showed a sum value >90. Among the patients who were clinically diagnosed to have multiple primary lung cancers and intrapulmonary metastasis, the 5-year survival of 70 patients who had a sum value of the differences in their 4 protein expression ratios, either >90 (newly classified multiple primary lung cancers) and <= 90 (newly classified intrapulmonary metastasis), were 81.1% and 40.2%, respectively (P = .002). CONCLUSIONS: The profile of protein expression in cancer-related genes is, thus, considered to be a useful tool for distinguishing multiple primary lung cancers from intrapulmonary metastasis and for determining the appropriate biological staging of lung cancer Cancer 2009;115:3489-500. (C) 2009 American Cancer Society.