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.
Pleomorphic carcinoma of the lung EGFR mutation EGFR-TKI
This is a preview of subscription content, log in to check access.
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.
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 350:2129–2139PubMedCrossRefGoogle Scholar
Paez JG, Janne PA, Lee JC et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500PubMedCrossRefGoogle Scholar
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 101:13306–13311PubMedCrossRefGoogle Scholar
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 23:3227–3234PubMedCrossRefGoogle Scholar
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–4420sPubMedCrossRefGoogle Scholar
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 94:896–903PubMedCrossRefGoogle Scholar
Kobayashi S, Boggon TJ, Dayaram T et al (2005) EGFR mutation, resistance of non-small-cell lung cancer to gefitinib. New Engl J Med 352:786–792PubMedCrossRefGoogle Scholar
Engelman JA, Zejnullahu K, Mitsudomi T et al (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316:1039–1043PubMedCrossRefGoogle Scholar
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 104:20932–20937PubMedCrossRefGoogle Scholar
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 68:9479–9487PubMedCrossRefGoogle Scholar
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 97:642–648PubMedCrossRefGoogle Scholar
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 97:778–784PubMedCrossRefGoogle Scholar
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 39:267–270PubMedCrossRefGoogle Scholar
Kaira K, Horie Y, Ayabe E et al (2010) Pulmonary pleomorphic carcinoma: a clinicopathological study including EGFR mutation analysis. J Thorac Oncol 5:460–465PubMedCrossRefGoogle Scholar
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 118:1588–1590PubMedCrossRefGoogle Scholar
Tatematsu A, Shimizu J, Murakami Y et al (2008) Epidermal growth factor receptor mutations in small cell lung cancer. Clin Cancer Res 14:6092–6096PubMedCrossRefGoogle Scholar