The clinicopathological significance of ALK rearrangements and KRAS and EGFR mutations in primary pulmonary mucinous adenocarcinoma
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Primary pulmonary mucinous adenocarcinoma (PPMA) is one of the important subtypes of lung adenocarcinoma. Detection of anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements and of KRAS and epidermal growth factor receptor (EGFR) mutations will help in diagnosing and predicting treatment outcome. The aim of this study was to investigate the clinicopathological significance of ALK rearrangements, KRAS and EGFR mutations in PPMA. ALK expression was detected immunohistochemically. KRAS and EGFR mutations were determined by the amplification refractory mutation system. Seventy-three patients of PPMA were enrolled. ALK rearrangements were detected in 34.2 % of patients and were more frequent in upper/middle lobe, stage III-IV, lymphatic permeation-positive patients and non-smokers. ALK rearrangements were significantly increased in the solid tumor predominant with mucin production subtype, and in special tissue structures, including signet ring cells, cribriform, and micropapillary patterns. KRAS mutations were observed in 23.3 % of patients and were more prevalent in invasive mucinous adenocarcinoma and lower lobe tumors. Only one case of ALK rearrangements harbored KRAS mutation, and no cases manifested with the coexistence of ALK rearrangements and EGFR mutations. KRAS and EGFR co-mutation was detected in one case. PPMA patients with ALK rearrangements or KRAS mutation represent a unique subtype in NSCLC. The results provide basis data for target therapy screening of PPMA patients.
KeywordsEGFR KRAS ALK rearrangements PPMA
This study was supported by a grant from the Magor Programs of Beijing Municipal Science and Technology Commission (D141100000214003).
Conceived and designed the experiments: Haiqing Zhang, Lixin Wei, and Yang Qu. Performed the experiments: Yang Qu and Nanying Che. Analyzed the data: Yang Qu, Nanying Che, and Dan Zhao. Contributed reagents/materials/analysis tools: Chen Zhang, Dan Shu, and Lijuan Zhou. Wrote the paper: Yang Qu. Collecting data: Lili zhang, Chongli Wang, Li Zhang, and Chunling Yin.
Conflicts of interest
- 9.Keedy VL, Temin S, Somerfield MR, et al. American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. J Clin Oncol. 2011;29:2121–7.CrossRefPubMedGoogle Scholar
- 11.Eberhard DA, Johnson BE, Amler LC, et al. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol. 2005;23:5900–9.CrossRefPubMedGoogle Scholar
- 15.Solomon B, Varella-Garcia M, Camidge DR. ALK gene rearrangements: a new therapeutic target in a molecularly defined subset of non-small cell lung cancer. J ThoracOncol. 2009;4:1450–4.Google Scholar
- 27.Kim H, Jang SJ, Chung DH, et al. A comprehensive comparative analysis of the histomorphological features of ALK-rearranged lung adenocarcinoma based on driver oncogene mutations: frequent expression of epithelial–mesenchymal transition markers than other genotype. PLoS One. 2013;8:e76999.CrossRefPubMedPubMedCentralGoogle Scholar