Abstract
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective in prolonging progression-free survival time of patients with non-small cell lung carcinoma, typically adenocarcinoma, bearing some active EGFR mutations in their tumors. However, the close relationship between the EGFR mutations and pleomorphic carcinoma of the lung, which is a very rare type of primary lung cancer, has never been elucidated. We present a 60-year-old Japanese woman with pleomorphic carcinoma of the lung that became resistant to cytotoxic chemotherapies including platinum-based chemotherapy, and her general condition seriously deteriorated. Thereafter, treatment with gefitinib was started and resulted in significant tumor shrinkage and a dramatic improvement in her general condition for up to 8.5 months. Analyses of the EGFR mutation in separately microdissected specimens from adenocarcinoma and spindle cell components revealed that both components possessed the L858R point mutation. These findings gave us some insight into the carcinogenesis of pleomorphic carcinoma of the lung in relation to EGFR gene alteration. Testing for EGFR mutation may be important in patients with advanced pleomorphic carcinoma including adenocarcinoma component that is usually chemoresistant.
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References
Lynch TJ, Bell DW, Sordella R et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. New Engl J Med 350:2129–2139
Paez JG, Janne PA, Lee JC et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500
Pao W, Miller V, Zakowski M et al (2004) EGF receptor gene mutations are common in lung cancers from “never smokers”, are associated with sensitivity of tumors to gefitinib, erlotinib. Proc Natl Acad Sci USA 101:13306–13311
Janne PA, Engelman JA, Johnson BE (2005) Epidermal growth factor receptor mutations in non-small-cell lung cancer: implications for treatment, tumor biology. J Clin Oncol 23:3227–3234
Janne PA, Johnson BE (2006) Effect of epidermal growth factor receptor tyrosine kinase domain mutations on the outcome of patients with non-small cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors. Clin Cancer Res 12:4416s–4420s
Sugio K, Uramoto H, Ono K et al (2006) Mutations within the tyrosine kinase domain of EGFR gene specifically occur in lung adenocarcinoma patients with a low exposure of tobacco smoking. Br J Cancer 94:896–903
Kobayashi S, Boggon TJ, Dayaram T et al (2005) EGFR mutation, resistance of non-small-cell lung cancer to gefitinib. New Engl J Med 352:786–792
Engelman JA, Zejnullahu K, Mitsudomi T et al (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316:1039–1043
Bean J, Brennan C, Shih J-Y et al (2007) MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci USA 104:20932–20937
Yano S, Wang W, Li Q et al (2008) Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations. Cancer Res 68:9479–9487
Kimura H, Fujiwara Y, Sone T et al (2006) High sensitivity detection of epidermal growth factor receptor mutations in the pleural effusion of non-small cell lung cancer patients. Cancer Sci 97:642–648
Kimura H, Suminoe M, Kasahara K et al (2007) Evaluation of epidermal growth factor receptor mutation status in serum DNA as a predictor of response to gefitinib (IRESSA). Br J Cancer 97:778–784
Hamburger A, Salmon S (1977) Primary bioassay of human tumor stem cells. Science 197:461–463
Reya T, Morrison SJ, Clarke MF et al (2001) Stem cells, cancer, cancer stem cells. Nature 414:105–111
Ushiki A, Koizumi T, Kobayashi N et al (2009) Genetic heterogeneity of EGFR mutation in pleomorphic carcinoma of the lung: response to gefitinib, clinical outcome. Jpn J Clin Oncol 39:267–270
Kaira K, Horie Y, Ayabe E et al (2010) Pulmonary pleomorphic carcinoma: a clinicopathological study including EGFR mutation analysis. J Thorac Oncol 5:460–465
Toyooka S, Yatabe Y, Tokumo M et al (2006) Mutations of epidermal growth factor receptor, K-ras genes in adenosquamous carcinoma of the lung. Int J Cancer 118:1588–1590
Tatematsu A, Shimizu J, Murakami Y et al (2008) Epidermal growth factor receptor mutations in small cell lung cancer. Clin Cancer Res 14:6092–6096
Acknowledgment
This work was financially supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Conflict of interest
Y. Takiguchi and K. Nishio received lecture fees from AstraZeneca, Japan, and Chugai Pharmaceutical, and received research grant from Chugai Pharmaceutical. The other authors have no conflict of interest to declare.
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Saitoh, M., Niijima, M., Takiguchi, Y. et al. An early event of EGFR mutation in pleomorphic carcinoma of the lung. Int J Clin Oncol 16, 770–773 (2011). https://doi.org/10.1007/s10147-011-0247-x
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DOI: https://doi.org/10.1007/s10147-011-0247-x