Clinicopathologic characteristics of EGFR, KRAS, and ALK alterations in 6,595 lung cancers

Oncotarget

Volumn 7, Issue 17, 2016, Pages 23874-23884

  Lee, Boram ^a,b   Lee, Taebum ^a   Lee, Se Hoon ^a,b   Choi, Yoon La ^a,b   Han, Joungho ^a  

^a Sungkyunkwan University School of Medicine   (South Korea)

^b Sungkyunkwan University   (South Korea)

Author keywords

ALK; EGFR; KRAS; Lung cancer; Molecular epidemiology

Indexed keywords

ANAPLASTIC LYMPHOMA KINASE; EPIDERMAL GROWTH FACTOR RECEPTOR; EGFR PROTEIN, HUMAN; KRAS PROTEIN, HUMAN; PROTEIN P21; PROTEIN TYROSINE KINASE; TUMOR MARKER;

ADULT; AGED; ALK GENE; ARTICLE; CLINICAL ARTICLE; CLINICAL FEATURE; DISEASE ASSOCIATION; EGFR GENE; EXON; FEMALE; GENE DELETION; GENE EXPRESSION; GENE MUTATION; GENE REARRANGEMENT; HUMAN; KOREA; MALE; MIDDLE AGED; MOLECULAR EPIDEMIOLOGY; MUTATIONAL ANALYSIS; NON SMALL CELL LUNG CANCER; ONCOGENE K RAS; POINT MUTATION; RETROSPECTIVE STUDY; SEX DIFFERENCE; VERY ELDERLY; ADENOCARCINOMA; CASE CONTROL STUDY; FOLLOW UP; GENETICS; LUNG TUMOR; PATHOLOGY; PROGNOSIS; SURVIVAL RATE;

ADENOCARCINOMA; ADULT; AGED; AGED, 80 AND OVER; BIOMARKERS, TUMOR; CARCINOMA, NON-SMALL-CELL LUNG; CASE-CONTROL STUDIES; FEMALE; FOLLOW-UP STUDIES; HUMANS; LUNG NEOPLASMS; MALE; MIDDLE AGED; POINT MUTATION; PROGNOSIS; PROTO-ONCOGENE PROTEINS P21(RAS); RECEPTOR PROTEIN-TYROSINE KINASES; RECEPTOR, EPIDERMAL GROWTH FACTOR; SURVIVAL RATE;

EID: 84966655564     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.8074     Document Type: Article

References (56)

1. Cancer Genome Atlas Research N. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014; 511:543-550.
2. Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Janne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010; 363:1693-1703.
3. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004; 304:1497-1500.
4. Choi YL, Sun JM, Cho J, Rampal S, Han J, Parasuraman B, Guallar E, Lee G, Lee J, Shim YM. EGFR mutation testing in patients with advanced non-small cell lung cancer: a comprehensive evaluation of real-world practice in an East Asian tertiary hospital. PLoS One. 2013; 8:e56011.
5. Lee DH, Srimuninnimit V, Cheng R, Wang X, Orlando M. Epidermal Growth Factor Receptor Mutation Status in the Treatment of Non-small Cell Lung Cancer: Lessons Learned. Cancer Res Treat. 2015; 47:549-554.
6. Lindeman NI, Cagle PT, Beasley MB, Chitale DA, Dacic S, Giaccone G, Jenkins RB, Kwiatkowski DJ, Saldivar JS, Squire J, Thunnissen E, Ladanyi M. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Thorac Oncol. 2013; 8:823-859.
7. Dogan S, Shen R, Ang DC, Johnson ML, D'Angelo SP, Paik PK, Brzostowski EB, Riely GJ, Kris MG, Zakowski MF, Ladanyi M. Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers. Clin Cancer Res. 2012; 18:6169-6177.
8. Bae NC, Chae MH, Lee MH, Kim KM, Lee EB, Kim CH, Park TI, Han SB, Jheon S, Jung TH, Park JY. EGFR, ERBB2, and KRAS mutations in Korean non-small cell lung cancer patients. Cancer Genet Cytogenet. 2007; 173:107-113.
9. Shi Y, Au JS, Thongprasert S, Srinivasan S, Tsai CM, Khoa MT, Heeroma K, Itoh Y, Cornelio G, Yang PC. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol. 2014; 9:154-162.
10. Girard N, Sima CS, Jackman DM, Sequist LV, Chen H, Yang JC, Ji H, Waltman B, Rosell R, Taron M, Zakowski MF, Ladanyi M, Riely G, Pao W. Nomogram to predict the presence of EGFR activating mutation in lung adenocarcinoma. Eur Respir J. 2012; 39:366-372.
11. Kim HJ, Choi EY, Jin HJ, Shin KC. Relationship between EGFR mutations and clinicopathological features of lung adenocarcinomas diagnosed via small biopsies. Anticancer Res. 2014; 34:3189-3195.
12. Motoi N, Szoke J, Riely GJ, Seshan VE, Kris MG, Rusch VW, Gerald WL, Travis WD. Lung adenocarcinoma: Modification of the 2004 WHO mixed subtype to include the major histologic subtype suggests correlations between papillary and micropapillary adenocarcinoma subtypes, EGFR mutations and gene expression analysis. American Journal of Surgical Pathology. 2008; 32A:810-827.
13. Ninomiya H, Hiramatsu M, Inamura K, Nomura K, Okui M, Miyoshi T, Okumura S, Satoh Y, Nakagawa K, Nishio M, Horai T, Miyata S, Tsuchiya E, Fukayama M, Ishikawa Y. Correlation between morphology and EGFR mutations in lung adenocarcinomas: Significance of the micropapillary pattern and the hobnail cell type. Lung Cancer. 2009; 63:235-240.
14. Sun PL, Seol H, Lee HJ, Yoo SB, Kim H, Xu X, Jheon S, Lee CT, Lee JS, Chung JH. High incidence of EGFR mutations in Korean men smokers with no intratumoral heterogeneity of lung adenocarcinomas: correlation with histologic subtypes, EGFR/TTF-1 expressions, and clinical features. J Thorac Oncol. 2012; 7:323-330.
15. Blons H, Cote JF, Le Corre D, Riquet M, Fabre-Guilevin E, Laurent-Puig P, Danel C. Epidermal growth factor receptor mutation in lung cancer are linked to bronchioloalveolar differentiation. Am J Surg Pathol. 2006; 30:1309-1315.
16. Ha SY, Choi SJ, Cho JH, Choi HJ, Lee J, Jung K, Irwin D, Liu X, Lira ME, Mao M, Kim HK, Choi YS, Shim YM, et al. Lung cancer in never-smoker Asian females is driven by oncogenic mutations, most often involving EGFR. Oncotarget. 2015; 6:5465-5474.
17. Finberg KE, Sequist LV, Joshi VA, Muzikansky A, Miller JM, Han M, Beheshti J, Chirieac LR, Mark EJ, Iafrate AJ. Mucinous differentiation correlates with absence of EGFR mutation and presence of KRAS mutation in lung adenocarcinomas with bronchioloalveolar features. J Mol Diagn. 2007; 9:320-326.
18. Choi YH, Lee JK, Kang HJ, Lee TS, Kim HR, Kim CH, Koh JS, Baek HJ, Lee JC, Na, II. Association between age at diagnosis and the presence of EGFR mutations in female patients with resected non-small cell lung cancer. J Thorac Oncol. 2010; 5:1949-1952.
19. Ueno T, Toyooka S, Suda K, Soh J, Yatabe Y, Miyoshi S, Matsuo K, Mitsudomi T. Impact of age on epidermal growth factor receptor mutation in lung cancer. Lung Cancer. 2012; 78:207-211.
20. Zhang Y, Sun Y, Pan Y, Li C, Shen L, Li Y, Luo X, Ye T, Wang R, Hu H, Li H, Wang L, Pao W, Chen H. Frequency of Driver Mutations in Lung Adenocarcinoma from Female Never-Smokers Varies with Histologic Subtypes and Age at Diagnosis. Clinical Cancer Research. 2012; 18:1947-1953.
21. Li H, Pan Y, Li Y, Li C, Wang R, Hu H, Zhang Y, Ye T, Wang L, Shen L, Sun Y, Chen H. Frequency of well-identified oncogenic driver mutations in lung adenocarcinoma of smokers varies with histological subtypes and graduated smoking dose. Lung Cancer. 2013; 79:8-13.
22. Tam IY, Chung LP, Suen WS, Wang E, Wong MC, Ho KK, Lam WK, Chiu SW, Girard L, Minna JD, Gazdar AF, Wong MP. Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features. Clin Cancer Res. 2006; 12:1647-1653.
23. Dacic S, Shuai Y, Yousem S, Ohori P, Nikiforova M. Clinicopathological predictors of EGFR/KRAS mutational status in primary lung adenocarcinomas. Mod Pathol. 2009; 23:159-168.
24. Rekhtman N, Ang DC, Riely GJ, Ladanyi M, Moreira AL. KRAS mutations are associated with solid growth pattern and tumor-infiltrating leukocytes in lung adenocarcinoma. Mod Pathol. 2013; 26:1307-1319.
25. Inamura K, Takeuchi K, Togashi Y, Hatano S, Ninomiya H, Motoi N, Mun M-y, Sakao Y, Okumura S, Nakagawa K, Soda M, Lim Choi Y, Mano H, Ishikawa Y. EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset. Mod Pathol. 2009; 22:508-515.
26. Kim HR, Shim HS, Chung J-H, Lee YJ, Hong YK, Rha SY, Kim SH, Ha S-J, Kim SK, Chung KY, Soo R, Kim JH, Cho BC. Distinct clinical features and outcomes in neversmokers with nonsmall cell lung cancer who harbor EGFR or KRAS mutations or ALK rearrangement. Cancer. 2012; 118:729-739.
27. Li Y, Li Y, Yang T, Wei S, Wang J, Wang M, Wang Y, Zhou Q, Liu H, Chen J. Clinical significance of EML4-ALK fusion gene and association with EGFR and KRAS gene mutations in 208 Chinese patients with non-small cell lung cancer. PLoS One. 2013; 8:e52093.
28. Rodig SJ, Mino-Kenudson M, Dacic S, Yeap BY, Shaw A, Barletta JA, Stubbs H, Law K, Lindeman N, Mark E, Janne PA, Lynch T, Johnson BE, Iafrate AJ, Chirieac LR. Unique clinicopathologic features characterize ALKrearranged lung adenocarcinoma in the western population. Clin Cancer Res. 2009; 15:5216-5223.
29. Wong DW, Leung EL, So KK, Tam IY, Sihoe AD, Cheng LC, Ho KK, Au JS, Chung LP, Pik Wong M. The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer. 2009; 115:1723-1733.
30. Nishino M, Klepeis VE, Yeap BY, Bergethon K, Morales-Oyarvide V, Dias-Santagata D, Yagi Y, Mark EJ, Iafrate AJ, Mino-Kenudson M. Histologic and cytomorphologic features of ALK-rearranged lung adenocarcinomas. Mod Pathol. 2012; 25:1462-1472.
31. Li Y, Pan Y, Wang R, Sun Y, Hu H, Shen X, Lu Y, Shen L, Zhu X, Chen H. ALK-rearranged lung cancer in Chinese: a comprehensive assessment of clinicopathology, IHC, FISH and RT-PCR. PLoS One. 2013; 8:e69016.
32. Takahashi T, Sonobe M, Kobayashi M, Yoshizawa A, Menju T, Nakayama E, Mino N, Iwakiri S, Sato K, Miyahara R, Okubo K, Manabe T, Date H. Clinicopathologic Features of Non-Small-Cell Lung Cancer with EML4-ALK Fusion Gene. Annals of Surgical Oncology. 2010; 17:889-897.
33. Paik JH, Choi CM, Kim H, Jang SJ, Choe G, Kim DK, Kim HJ, Yoon H, Lee CT, Jheon S, Choe JY, Chung JH. Clinicopathologic implication of ALK rearrangement in surgically resected lung cancer: a proposal of diagnostic algorithm for ALK-rearranged adenocarcinoma. Lung Cancer. 2012; 76:403-409.
34. Shaw AT, Yeap BY, Mino-Kenudson M, Digumarthy SR, Costa DB, Heist RS, Solomon B, Stubbs H, Admane S, McDermott U, Settleman J, Kobayashi S, Mark EJ, et al. Clinical Features and Outcome of Patients With Non-Small-Cell Lung Cancer Who Harbor EML4-ALK. Journal of Clinical Oncology. 2009; 27:4247-4253.
35. Gainor JF, Varghese AM, Ou SH, Kabraji S, Awad MM, Katayama R, Pawlak A, Mino-Kenudson M, Yeap BY, Riely GJ, Iafrate AJ, Arcila ME, Ladanyi M, et al. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer. Clin Cancer Res. 2013; 19:4273-4281.
36. Koivunen JP, Mermel C, Zejnullahu K, Murphy C, Lifshits E, Holmes AJ, Choi HG, Kim J, Chiang D, Thomas R, Lee J, Richards WG, Sugarbaker DJ, et al. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res. 2008; 14:4275-4283.
37. Kuo YW, Wu SG, Ho CC, Shih JY. Good response to gefitinib in lung adenocarcinoma harboring coexisting EML4-ALK fusion gene and EGFR mutation. J Thorac Oncol. 2010; 5:2039-2040.
38. Zhang X, Zhang S, Yang X, Yang J, Zhou Q, Yin L, An S, Lin J, Chen S, Xie Z, Zhu M, Wu YL. Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression. Mol Cancer. 2010; 9:188.
39. Li S, Li L, Zhu Y, Huang C, Qin Y, Liu H, Ren-Heidenreich L, Shi B, Ren H, Chu X, Kang J, Wang W, Xu J, et al. Coexistence of EGFR with KRAS, or BRAF, or PIK3CA somatic mutations in lung cancer: a comprehensive mutation profiling from 5125 Chinese cohorts. Br J Cancer. 2014; 110:2812-2820.
40. Popat S, Vieira de Araújo A, Min T, Swansbury J, Dainton M, Wotherspoon A, Lim E, Nicholson AG, O'Brien MER. Lung Adenocarcinoma with Concurrent Exon 19 EGFR Mutation and ALK Rearrangement Responding to Erlotinib. Journal of Thoracic Oncology. 2011; 6:1962-1963.
41. Rossing HH, Grauslund M, Urbanska EM, Melchior LC, Rask CK, Costa JC, Skov BG, Sorensen JB, Santoni-Rugiu E. Concomitant occurrence of EGFR (epidermal growth factor receptor) and KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in an ALK (anaplastic lymphoma kinase)-positive lung adenocarcinoma patient with acquired resistance to crizotinib: a case report. BMC Res Notes. 2013; 6:489.
42. Takeda M, Okamoto I, Fujita Y, Arao T, Ito H, Fukuoka M, Nishio K, Nakagawa K. De novo resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in EGFR mutation-positive patients with non-small cell lung cancer. J Thorac Oncol. 2010; 5:399-400.
43. Tiseo M, Gelsomino F, Boggiani D, Bortesi B, Bartolotti M, Bozzetti C, Sammarelli G, Thai E, Ardizzoni A. EGFR and EML4-ALK gene mutations in NSCLC: A case report of erlotinib-resistant patient with both concomitant mutations. Lung Cancer. 2011; 71:241-243.
44. Lee B, Lee B, Han G, Kwon MJ, Han J, Choi YL. KRAS Mutation Detection in Non-small Cell Lung Cancer Using a Peptide Nucleic Acid-Mediated Polymerase Chain Reaction Clamping Method and Comparative Validation with Next-Generation Sequencing. Korean J Pathol. 2014; 48:100-107.
45. Kim HJ, Lee KY, Kim Y-C, Kim K-S, Lee SY, Jang TW, Lee MK, Shin K-C, Lee GH, Lee JC, Lee JE, Kim SY. Detection and comparison of peptide nucleic acid-mediated real-time polymerase chain reaction clamping and direct gene sequencing for epidermal growth factor receptor mutations in patients with non-small cell lung cancer. Lung Cancer. 2012; 75:321-325.
46. Ha SY, Han J, Lee JJ, Kim YE, Choi Y-L, Kim HK. Mucoepidermoid Carcinoma of Tracheobronchial Tree: Clinicopathological Study of 31 Cases. The Korean Journal of Pathology. 2011; 45:175.
47. Sun JM, Lira M, Pandya K, Choi YL, Ahn JS, Mao M, Han J, Park K, Ahn MJ, Kim J. Clinical characteristics associated with ALK rearrangements in never-smokers with pulmonary adenocarcinoma. Lung Cancer. 2014; 83:259-264.
48. Lee SH, Kim WS, Choi YD, Seo JW, Han JH, Kim MJ, Kim L, Lee GK, Lee CH, Oh MH, Kim GY, Sung SH, Lee KY, et al. Analysis of Mutations in Epidermal Growth Factor Receptor Gene in Korean Patients with Non-small Cell Lung Cancer: Summary of a Nationwide Survey. J Pathol Transl Med. 2015.
49. Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, Kris MG, Varmus H. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2005; 2:e73.
50. Inukai M, Toyooka S, Ito S, Asano H, Ichihara S, Soh J, Suehisa H, Ouchida M, Aoe K, Aoe M, Kiura K, Shimizu N, Date H. Presence of epidermal growth factor receptor gene T790M mutation as a minor clone in non-small cell lung cancer. Cancer Res. 2006; 66:7854-7858.
51. Lee Y, Lee GK, Hwang JA, Yun T, Kim HT, Lee JS. Clinical likelihood of sporadic primary EGFR T790M mutation in EGFR-mutant lung cancer. Clin Lung Cancer. 2015; 16:46-50.
52. Falini B, Bigerna B, Fizzotti M, Pulford K, Pileri SA, Delsol G, Carbone A, Paulli M, Magrini U, Menestrina F, Giardini R, Pilotti S, Mezzelani A, et al. ALK Expression Defines a Distinct Group of T/Null Lymphomas ("ALK Lymphomas") with a Wide Morphological Spectrum. The American Journal of Pathology. 1998; 153:875-886.
53. Lawrence B, Perez-Atayde A, Hibbard MK, Rubin BP, Dal Cin P, Pinkus JL, Pinkus GS, Xiao S, Yi ES, Fletcher CDM, Fletcher JA. TPM3-ALK and TPM4-ALK Oncogenes in Inflammatory Myofibroblastic Tumors. The American Journal of Pathology. 2000; 157:377-384.
54. Cai W, Lin D, Wu C, Li X, Zhao C, Zheng L, Chuai S, Fei K, Zhou C, Hirsch FR. Intratumoral Heterogeneity of ALK-Rearranged and ALK/EGFR Coaltered Lung Adenocarcinoma. J Clin Oncol. 2015.
55. Girard N, Deshpande C, Azzoli CG, Rusch VW, Travis WD, Ladanyi M, Pao W. Use of epidermal growth factor receptor/Kirsten rat sarcoma 2 viral oncogene homolog mutation testing to define clonal relationships among multiple lung adenocarcinomas: comparison with clinical guidelines. Chest. 2010; 137:46-52.
56. Ellison G, Zhu G, Moulis A, Dearden S, Speake G, McCormack R. EGFR mutation testing in lung cancer: a review of available methods and their use for analysis of tumour tissue and cytology samples. J Clin Pathol. 2013; 66:79-89.