Molecular pathology of pulmonary carcinomas
Authors:
Zdeněk Rohan 1,2; Milada Matějčková 1; Radoslav Matěj 1,2
Authors place of work:
Oddělení patologie a molekulární medicíny, Thomayerova nemocnice, Praha
1; Ústav patologie, Univerzita Karlova v Praze, 3. lékařská fakulta
2
Published in the journal:
Čes.-slov. Patol., 50, 2014, No. 2, p. 71-75
Category:
Reviews Article
Summary
The group of non–small cell lung carcinomas includes tumors that are variable at the clinical, histopathological and molecular levels. Advances in the understanding of molecular pathology of lung adenocarcinomas in particular has led to changes in their histopathological classification and treatment. Patients diagnosed with lung adenocarcinoma harboring specific mutations benefit from the administration of specific targeted therapy. Therefore, pathologists closely involved in the diagnostics of lung tumors significantly contribute to the diagnostic-therapeutical algorithm. Analysis of EGFR gene mutations in lung adenocarcinomas is already routinely performed and the presence of activating mutations in EGFR is the main indication for the administration of tyrosinkinase inhibitors. Besides EGFR mutations, EML4–ALK rearrangement is also being analysed and there is potential in analysing BRAF mutations as well. The aim of this review is to summarize the role of the most relevant molecules that also serve as the therapeutic target for practicing pathologists.
Keywords:
NSCLC – lung adenocarcinoma – EGFR – ALK – BRAF – KRAS – RET – MET – erlotinib – gefitinib – crizotinib
Zdroje
1. Roskoski R Jr. The ErbB/HER family of protein-tyrosine kinases and cancer. Pharmacol Res 2013; 79C: 34-74.
2. Shigematsu H, Lin L, Takahashi T, et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 2005; 97(5): 339-346.
3. Yousem SA. Role of molecular studies in the diagnosis of lung adenocarcinoma. Mod Pathol 2012; 25 Suppl 1S11-17.
4. Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005; 2(3): e73.
5. Kobayashi S, Boggon TJ, Dayaram T, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 2005; 352(8): 786-792.
6. Bean J, Brennan C, Shih JY, et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci U S A 2007; 104(52): 20932-20937.
7. Zakowski MF, Hussain S, Pao W, et al. Morphologic features of adenocarcinoma of the lung predictive of response to the epidermal growth factor receptor kinase inhibitors erlotinib and gefitinib. Arch Pathol Lab Med 2009; 133(3): 470-477.
8. Sartori G, Cavazza A, Sgambato A, et al. EGFR and K-ras mutations along the spectrum of pulmonary epithelial tumors of the lung and elaboration of a combined clinicopathologic and molecular scoring system to predict clinical responsiveness to EGFR inhibitors. Am J Clin Pathol 2009; 131(4): 478-489.
9. Rekhtman N, Ang DC, Riely GJ, Ladanyi M and Moreira AL. KRAS mutations are associated with solid growth pattern and tumor-infiltrating leukocytes in lung adenocarcinoma. Mod Pathol 2013; 26(10): 1307-1319.
10. Allo G, Bandarchi B, Yanagawa N, et al. Epidermal growth factor receptor mutation-specific immunohistochemical antibodies in lung adenocarcinoma. Histopathology 2013; 20. doi: 10.1111/his.12331. [Epub ahead of print]
11. Isaksson S, Bendahl PO, Salomonsson A, et al. Detecting EGFR alterations in clinical specimens-pitfalls and necessities. Virchows Arch 2013; 463(6): 755-764.
12. Wen YH, Brogi E, Hasanovic A, et al. Immunohistochemical staining with EGFR mutation-specific antibodies: high specificity as a diagnostic marker for lung adenocarcinoma. Mod Pathol 2013; 26(9): 1197-1203.
13. Lawrence B, Perez-Atayde A, Hibbard MK, et al. TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors. Am J Pathol 2000; 157(2): 377-384.
14. Griffin CA, Hawkins AL, Dvorak C, Henkle C, Ellingham T and Perlman EJ. Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors. Cancer Res 1999; 59(12): 2776-2780.
15. Debelenko LV, Raimondi SC, Daw N, et al. Renal cell carcinoma with novel VCL-ALK fusion: new representative of ALK-associated tumor spectrum. Mod Pathol 2011; 24(3): 430-442.
16. Horn L and Pao W. EML4-ALK: honing in on a new target in non-small-cell lung cancer. J Clin Oncol 2009; 27(26): 4232-4235.
17. Inamura K, Takeuchi K, Togashi Y, et al. EML4-ALK Fusion Is Linked to Histological Characteristics in a Subset of Lung Cancers. Journal of Thoracic Oncology 2008; 3(1): 13-17.
18. Rodig SJ, Mino-Kenudson M, Dacic S, et al. Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population. Clin Cancer Res 2009; 15(16): 5216-5223.
19. Inamura K, Takeuchi K, Togashi Y, et al. 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(4): 508-515.
20. Popat S, Gonzalez D, Min T, et al. ALK translocation is associated with ALK immunoreactivity and extensive signet-ring morphology in primary lung adenocarcinoma. Lung Cancer 2012; 75(3): 300-305.
21. Yoshida A, Tsuta K, Watanabe S, et al. Frequent ALK rearrangement and TTF-1/p63 co-expression in lung adenocarcinoma with signet-ring cell component. Lung Cancer 2011; 72(3): 309-315.
22. To KF, Tong JH, Yeung KS, et al. Detection of ALK rearrangement by immunohistochemistry in lung adenocarcinoma and the identification of a novel EML4-ALK variant. J Thorac Oncol 2013; 8(7): 883-891.
23. Han XH, Zhang NN, Ma L, et al. Immunohistochemistry reliably detects ALK rearrangements in patients with advanced non-small-cell lung cancer. Virchows Arch 2013; 463(4): 583-591.
24. Mino-Kenudson M, Chirieac LR, Law K, et al. A novel, highly sensitive antibody allows for the routine detection of ALK-rearranged lung adenocarcinomas by standard immunohistochemistry. Clin Cancer Res 2010; 16(5): 1561-1571.
25. Shaw AT, Kim D-W, Nakagawa K, et al. Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer. New England Journal of Medicine 2013; 368(25): 2385-2394.
26. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417(6892): 949-954.
27. Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE and Fagin JA. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res 2003; 63(7): 1454-1457.
28. Paik PK, Arcila ME, Fara M, et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol 2011; 29(15): 2046-2051.
29. Chetty R and Govender D. Gene of the month: KRAS. J Clin Pathol 2013; 66(7): 548-550.
30. Sun JM, Hwang DW, Ahn JS, Ahn MJ and Park K. Prognostic and predictive value of KRAS mutations in advanced non-small cell lung cancer. PLoS One 2013; 8(5): e64816.
31. Riely GJ, Marks J and Pao W. KRAS mutations in non-small cell lung cancer. Proc Am Thorac Soc 2009; 6(2): 201-205.
32. Lindeman NI, Cagle PT, Beasley MB, et al. 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(7): 823-859.
33. Kohno T, Ichikawa H, Totoki Y, et al. KIF5B-RET fusions in lung adenocarcinoma. Nat Med 2012; 18(3): 375-377.
34. Pan ZW and Li JC. Advances in molecular genetics of Hirschsprung’s disease. Anat Rec (Hoboken) 2012; 295(10): 1628-1638.
35. Takeuchi K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nat Med 2012; 18(3): 378-381.
36. Drilon A, Rekhtman N, Ladanyi M and Paik P. Squamous-cell carcinomas of the lung: emerging biology, controversies, and the promise of targeted therapy. Lancet Oncol 2012; 13(10): e418-426.
37. Kim HS, Mitsudomi T, Soo RA and Cho BC. Personalized therapy on the horizon for squamous cell carcinoma of the lung. Lung Cancer 2013; 80(3): 249-255.
38. Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011; 6(2): 244-285.
Štítky
Anatomical pathology Forensic medical examiner ToxicologyČlánok vyšiel v časopise
Czecho-Slovak Pathology
2014 Číslo 2
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