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Role of Immunohistochemistry in the Detection of Targetable Mutations

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Diagnosing Non-small Cell Carcinoma in Small Biopsy and Cytology

Abstract

Testing for EGFR gene mutations and ALK rearrangements has entered everyday clinical practice for the management of patients with pulmonary adenocarcinoma. With the development of more sensitive molecular techniques to detect specific mutations, small biopsy and cytologic specimens are being used more frequently for diagnostic work-up and molecular characterization of lung carcinoma. Molecular testing, however, is not widely offered due to cost constraints and technical complexity, including highly skilled and trained personnel to perform and interpret the results. Despite suitability of small biopsy and cytologic material for molecular tests, samples are periodically inadequate for molecular tests. Therefore, immunohistochemical stains offer the potential to detect mutant proteins as an alternative or adjunct to molecular techniques thereby expanding availability of molecular characterization of tumors.

Most laboratories have the infrastructure to perform immunohistochemical tests, and pathologists are familiar with interpretation and reporting of the tests. In addition, the results are typically available within 24 h in most laboratories as opposed to the more time-consuming molecular tests. More importantly, mutation-specific antibodies can play a significant role when diagnostic material is unsatisfactory for molecular testing due to low tumor content or decalcification, as in cases of bone biopsies. A positive immunohistochemical result could avoid re-biopsy of the patient for procurement of additional tissue for mutation analysis.

This chapter discusses the clinical utility and efficacy of immunohistochemical markers for detecting specific molecular alterations in small biopsy material.

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References

  1. 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;8:823–59.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  2. Molina JR, Adjei AA, Jett JR. Advances in chemotherapy of non-small cell lung cancer. Chest. 2006;130:1211–9.

    Article  PubMed  CAS  Google Scholar 

  3. 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;6:244–85.

    Article  PubMed  Google Scholar 

  4. Edwards SL, Roberts C, McKean ME, et al. Preoperative histological classification of primary lung cancer: accuracy of diagnosis and use of the non-small cell category. J Clin Pathol. 2000;53:537–40.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  5. Rekhtman N, Ang DC, Sima CS, et al. Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens. Mod Pathol. 2011;24:1348–59.

    Article  PubMed  Google Scholar 

  6. Mukhopadhyay S, Katzenstein ALA. Subclassification of Non-small Cell Lung Carcinomas Lacking Morphologic Differentiation on Biopsy Specimens: Utility of an Immunohistochemical Panel Containing TTF-1, Napsin A, p63, and CK5/6. Am J Surg Pathol. 2011;35:15–25.

    Article  PubMed  Google Scholar 

  7. Nicholson AG, Gonzalez D, Shah P, et al. Refining the diagnosis and EGFR status of non-small cell lung carcinoma in biopsy and cytologic material, using a panel of mucin staining, TTF-1, cytokeratin 5/6, and P63, and EGFR mutation analysis. J Thorac Oncol. 2010;5:436–41.

    Article  PubMed  Google Scholar 

  8. Travis WD, Rekhtman N, Riley GJ, et al. Pathologic diagnosis of advanced lung cancer based on small biopsies and cytology: a paradigm shift. J Thorac Oncol. 2010;5:411–4.

    Article  PubMed  Google Scholar 

  9. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129–39.

    Article  PubMed  CAS  Google Scholar 

  10. Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497–500.

    Article  PubMed  CAS  Google Scholar 

  11. Pao W, Miller V, Zakowski M, et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA. 2004;101:13306–11.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Sharma SV, Bell DW, Settleman J, et al. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer. 2007;7:169–81.

    Article  PubMed  CAS  Google Scholar 

  13. Sequist LV, Bell DW, Lynch TJ, et al. Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer. J Clin Oncol. 2007;25:587–95.

    Article  PubMed  CAS  Google Scholar 

  14. Li AR, Chitale D, Riely GJ, et al. EGFR mutations in lung adenocarcinomas: clinical testing experience and relationship to EGFR gene copy number and immunohistochemical expression. J Mol Diagn. 2008;10:242–8.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Rekhtman N, Brandt SM, Sigel CS, et al. Suitability of thoracic cytology for new therapeutic paradigms in non-small cell lung carcinoma: high accuracy of tumor subtyping and feasibility of EGFR and KRAS molecular testing. J Thorac Oncol. 2011;6:451–8.

    Article  PubMed  Google Scholar 

  16. Pan Q, Pao W, Ladanyi M. Rapid polymerase chain reaction-based detection of epidermal growth factor receptor gene mutations in lung adenocarcinomas. J Mol Diagn. 2005;7: 396–403.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  17. Lozano MD, Zulueta JJ, Echeveste JI, et al. Assessment of epidermal growth factor receptor and K-ras mutation status in cytological stained smears of non-small cell lung cancer patients: correlation with clinical outcomes. Oncologist. 2011;16:877–85.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. Smouse JH, Cibas ES, Janne PA, et al. EGFR mutations are detected comparably in cytologic and surgical pathology specimens of nonsmall cell lung cancer. Cancer. 2009;117:67–72.

    PubMed  Google Scholar 

  19. Schuurbiers OC, Looijen-Salamon MG, Ligtenberg MJ, et al. A brief retrospective report on the feasibility of epidermal growth factor receptor and KRAS mutation analysis in transesophageal ultrasound- and endobronchial ultrasound-guided fine needle cytological aspirates. J Thorac Oncol. 2010;5:1664–7.

    Article  PubMed  Google Scholar 

  20. Heymann J, Bulman WA, Maxfield RA, Powell CA, Halmos B, Sonett J, Beaubier NT, Crapanzano JP, Mansukhani MM, Saqi A. Molecular testing guidelines for lung adenocarcinomas: utility of cell blocks and concordance between fine needle aspiration cytology and histology samples. CytoJournal. 2014;11:12.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Nomoto K, Tsuta K, Takano T, et al. Detection of EGFR mutations in archived cytologic specimens of non-small cell lung cancer using high-resolution melting analysis. Am J Clin Pathol. 2006;126:608–15.

    Article  PubMed  CAS  Google Scholar 

  22. Boldrini L, Gisfredi S, Ursino S, et al. Mutational analysis in cytological specimens of advanced lung adenocarcinoma: a sensitive method for molecular diagnosis. J Thorac Oncol. 2007;2:1086–90.

    Article  PubMed  Google Scholar 

  23. Smith GD, Chadwick BE, Willmore-Payne C, et al. Detection of epidermal growth factor receptor gene mutations in cytology specimens from patients with non-small cell lung cancer utilising high-resolution melting amplicon analysis. J Clin Pathol. 2008;61:487–93.

    Article  PubMed  CAS  Google Scholar 

  24. Malapelle U, Bellevicine C, De Luca C, et al. EGFR mutations detected on cytology samples by a centralized laboratory reliably predict response to gefitinib in non-small cell lung carcinoma patients. Cancer Cytopathol. 2013;121:552–60.

    Article  PubMed  CAS  Google Scholar 

  25. Knoepp SM, Roh MH. Ancillary techniques on direct-smear aspirate slides: a significant evolution for cytopathology techniques. Cancer Cytopathol. 2013;121:120–8.

    Article  PubMed  CAS  Google Scholar 

  26. Khode R, Larsen DA, Culbreath BC, et al. Comparative study of epidermal growth factor receptor mutation analysis on cytology smears and surgical pathology specimens from primary and metastatic lung carcinomas. Cancer Cytopathol. 2013;121:361–9.

    Article  PubMed  CAS  Google Scholar 

  27. Bozzetti C, Naldi N, Nizzoli R, et al. Reliability of EGFR and KRAS mutation analysis on fine-needle aspiration washing in non-small cell lung cancer. Lung Cancer. 2013;80:35–8.

    Article  PubMed  Google Scholar 

  28. Ellis PM, Verma S, Sehdev S, et al. Challenges to implementation of an epidermal growth factor receptor testing strategy for non-small-cell lung cancer in a publicly funded health care system. J Thorac Oncol. 2013;8:1136–41.

    Article  PubMed  CAS  Google Scholar 

  29. Savic S, Tapia C, Grilli B, et al. Comprehensive epidermal growth factor receptor gene analysis from cytological specimens of non-small-cell lung cancers. Br J Cancer. 2008;98:154–60.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  30. Garcia-Olive I, Monso E, Andreo F, et al. Endobronchial ultrasound-guided transbronchial needle aspiration for identifying EGFR mutations. Eur Respir J. 2010;35:391–5.

    Article  PubMed  CAS  Google Scholar 

  31. Akagi K, Sakai H, Sudo J, et al. Simple method to detect important epodermal growth factor receptor gene mutations with bronchoscopic specimens of lung cancer patients for gefitinib treatment. Target Oncol. 2007;2:145–51.

    Article  Google Scholar 

  32. Hlinkova K, Babal P, Berzinec P, et al. Rapid and efficient detection of EGFR mutations in problematic cytologic specimens by high-resolution melting analysis. Mol Diagn Ther. 2011;15:21–9.

    Article  PubMed  CAS  Google Scholar 

  33. Ma ES, Ng WK, Wong CL. EGFR gene mutation study in cytology specimens. Acta Cytol. 2012;56:661–8.

    Article  PubMed  CAS  Google Scholar 

  34. Brevet M, Arcila M, Ladanyi M. Assessment of EGFR mutation status in lung adenocarcinoma by immunohistochemistry using antibodies specific to the two major forms of mutant EGFR. J Mol Diagn. 2010;12:169–76.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  35. Yu J, Kane S, Wu J, et al. Mutation-specific antibodies for the detection of EGFR mutations in non-small-cell lung cancer. Clin Cancer Res. 2009;15:3023–8.

    Article  PubMed  CAS  Google Scholar 

  36. Hasanovic A, Ang D, Moreira AL, et al. Use of mutation specific antibodies to detect EGFR status in small biopsy and cytology specimens of lung adenocarcinoma. Lung Cancer. 2012;77:299–305.

    Article  PubMed  Google Scholar 

  37. Kawahara A, Yamamoto C, Nakashima K, et al. Molecular diagnosis of activating EGFR mutations in non-small cell lung cancer using mutation-specific antibodies for immunohistochemical analysis. Clin Cancer Res. 2010;16:3163–70.

    Article  PubMed  CAS  Google Scholar 

  38. Kitamura A, Hosoda W, Sasaki E, et al. Immunohistochemical detection of EGFR mutation using mutation-specific antibodies in lung cancer. Clin Cancer Res. 2010;16:3349–55.

    Article  PubMed  CAS  Google Scholar 

  39. Kato Y, Peled N, Wynes MW, et al. Novel epidermal growth factor receptor mutation-specific antibodies for non-small cell lung cancer: immunohistochemistry as a possible screening method for epidermal growth factor receptor mutations. J Thorac Oncol. 2010;5:1551–8.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Kozu Y, Tsuta K, Kohno T, et al. The usefulness of mutation-specific antibodies in detecting epidermal growth factor receptor mutations and in predicting response to tyrosine kinase inhibitor therapy in lung adenocarcinoma. Lung Cancer. 2011;73:45–50.

    Article  PubMed  Google Scholar 

  41. Nakamura H, Mochizuki A, Shinmyo T, et al. Immunohistochemical detection of mutated epidermal growth factor receptors in pulmonary adenocarcinoma. Anticancer Res. 2010;30: 5233–7.

    PubMed  Google Scholar 

  42. Simonetti S, Molina MA, Queralt C, et al. Detection of EGFR mutations with mutation-specific antibodies in stage IV non-small-cell lung cancer. J Transl Med. 2010;8:135.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Allo G, Bandarchi B, Yanagawa N, et al. Epidermal growth factor receptor mutation-specific immunohistochemical antibodies in lung adenocarcinoma. Histopathology. 2014;64(6):826–39.

    Article  PubMed  Google Scholar 

  44. Seo AN, Park TI, Jin Y, et al. Novel EGFR mutation-specific antibodies for lung adenocarcinoma: Highly specific but not sensitive detection of an E746_A750 deletion in exon 19 and an L858R mutation in exon 21 by immunohistochemistry. Lung Cancer. 2014;83(3):316–23.

    Article  PubMed  Google Scholar 

  45. Jiang G, Fan C, Zhang X, et al. Ascertaining an appropriate diagnostic algorithm using EGFR mutation-specific antibodies to detect EGFR status in non-small-cell lung cancer. PLoS One. 2013;8:e59183.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  46. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–57.

    Article  PubMed  CAS  Google Scholar 

  47. Kawahara A, Azuma K, Sumi A, et al. Identification of non-small-cell lung cancer with activating EGFR mutations in malignant effusion and cerebrospinal fluid: rapid and sensitive detection of exon 19 deletion E746-A750 and exon 21 L858R mutation by immunocytochemistry. Lung Cancer. 2011;74:35–40.

    Article  PubMed  Google Scholar 

  48. Kawahara A, Taira T, Azuma K, et al. A diagnostic algorithm using EGFR mutation-specific antibodies for rapid response EGFR-TKI treatment in patients with non-small cell lung cancer. Lung Cancer. 2012;78:39–44.

    Article  PubMed  Google Scholar 

  49. 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;26:1197–203.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  50. Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448:561–6.

    Article  PubMed  CAS  Google Scholar 

  51. 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;22:508–15.

    Article  PubMed  CAS  Google Scholar 

  52. Inamura K, Takeuchi K, Togashi Y, et al. EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers. J Thorac Oncol. 2008;3:13–7.

    Article  PubMed  Google Scholar 

  53. 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;15:5216–23.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  54. Jokoji R, Yamasaki T, Minami S, et al. Combination of morphological feature analysis and immunohistochemistry is useful for screening of EML4-ALK-positive lung adenocarcinoma. J Clin Pathol. 2010;63:1066–70.

    Article  PubMed  Google Scholar 

  55. Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol. 2009;27:4247–53.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  56. Pareja FG, Mansukhani M, Bulman WA, Saqi A. ALK rearrangement: salient morphological features on cytology and surgical pathology. Abstract. J Am Soc Cytopathol. 2013;2(1 Suppl):S60.

    Article  Google Scholar 

  57. Gainor JF, Varghese AM, Ou SH, 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;19:4273–81.

    Article  PubMed  CAS  Google Scholar 

  58. Yang J, Zhang XC, Su J, et al. Lung cancers with concomitant EGFR mutations and ALK rearrangements: diverse responses to EGFR-TKI and crizotinib in relation to diverse receptors phosphorylation. Clin Cancer Res. 2014;20(5):1383–92.

    Article  PubMed  CAS  Google Scholar 

  59. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363:1693–703.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  60. Shaw AT, Yeap BY, Solomon BJ, et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011;12:1004–12.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  61. Camidge DR, Kono SA, Flacco A, et al. Optimizing the detection of lung cancer patients harboring anaplastic lymphoma kinase (ALK) gene rearrangements potentially suitable for ALK inhibitor treatment. Clin Cancer Res. 2010;16:5581–90.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  62. Kim H, Yoo SB, Choe JY, et al. Detection of ALK gene rearrangement in non-small cell lung cancer: a comparison of fluorescence in situ hybridization and chromogenic in situ hybridization with correlation of ALK protein expression. J Thorac Oncol. 2011;6:1359–66.

    Article  PubMed  Google Scholar 

  63. Martelli MP, Sozzi G, Hernandez L, et al. EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues. Am J Pathol. 2009;174:661–70.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  64. 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;16:1561–71.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  65. Minca EC, Portier BP, Wang Z, et al. ALK status testing in non-small cell lung carcinoma: correlation between ultrasensitive IHC and FISH. J Mol Diagn. 2013;15:341–6.

    Article  PubMed  CAS  Google Scholar 

  66. Sakairi Y, Nakajima T, Yasufuku K, et al. EML4-ALK fusion gene assessment using metastatic lymph node samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration. Clin Cancer Res. 2010;16:4938–45.

    Article  PubMed  CAS  Google Scholar 

  67. Savic S, Bode B, Diebold J, et al. Detection of ALK-positive non-small-cell lung cancers on cytological specimens: high accuracy of immunocytochemistry with the 5A4 clone. J Thorac Oncol. 2013;8:1004–11.

    Article  PubMed  CAS  Google Scholar 

  68. Selinger CI, Rogers TM, Russell PA, et al. Testing for ALK rearrangement in lung adenocarcinoma: a multicenter comparison of immunohistochemistry and fluorescent in situ hybridization. Mod Pathol. 2013;26:1545–53.

    Article  PubMed  CAS  Google Scholar 

  69. Tsao MSH, Fred R, Yatabe Y. IASLC atlas of ALK testing in lung cancer. Aurora, CO: IASLC Press; 2013.

    Google Scholar 

  70. Sholl LM, Weremowicz S, Gray SW, et al. Combined use of ALK immunohistochemistry and FISH for optimal detection of ALK-rearranged lung adenocarcinomas. J Thorac Oncol. 2013;8:322–8.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  71. Bergethon K, Shaw AT, Ou SH, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012;30:863–70.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  72. Go H, Kim DW, Kim D, et al. Clinicopathologic analysis of ROS1-rearranged non-small-cell lung cancer and proposal of a diagnostic algorithm. J Thorac Oncol. 2013;8:1445–50.

    Article  PubMed  CAS  Google Scholar 

  73. Mescam-Mancini L, Lantuejoul S, Moro-Sibilot D, et al. On the relevance of a testing algorithm for the detection of ROS1-rearranged lung adenocarcinomas. Lung Cancer. 2014;83: 168–73.

    Article  PubMed  Google Scholar 

  74. Sholl LM, Sun H, Butaney M, et al. ROS1 immunohistochemistry for detection of ROS1-rearranged lung adenocarcinomas. Am J Surg Pathol. 2013;37:1441–9.

    Article  PubMed  Google Scholar 

  75. Kinno T, Tsuta K, Shiraishi K, et al. Clinicopathological features of nonsmall cell lung carcinomas with BRAF mutations. Ann Oncol. 2014;25:138–42.

    Article  PubMed  CAS  Google Scholar 

  76. Liu SV, Subramaniam D, Cyriac GC, et al. Emerging protein kinase inhibitors for non-small cell lung cancer. Expert Opin Emerg Drugs. 2014;19(1):51–65.

    Article  PubMed  CAS  Google Scholar 

  77. Ilie M, Lassalle S, Long-Mira E, et al. Diagnostic value of immunohistochemistry for the detection of the BRAFV600E mutation in papillary thyroid carcinoma. Comparative analysis with three DNA-based assays. Thyroid. 2014;24(5):858–66.

    Article  PubMed  CAS  Google Scholar 

  78. Ilie M, Long E, Hofman V, et al. Diagnostic value of immunohistochemistry for the detection of the BRAFV600E mutation in primary lung adenocarcinoma Caucasian patients. Ann Oncol. 2013;24:742–8.

    Article  PubMed  CAS  Google Scholar 

  79. Sasaki H, Shimizu S, Tani Y, et al. Usefulness of immunohistochemistry for the detection of the BRAF V600E mutation in Japanese lung adenocarcinoma. Lung Cancer. 2013;82:51–4.

    Article  PubMed  Google Scholar 

  80. Girard N, Deshpande C, Lau C, et al. Comprehensive histologic assessment helps to differentiate multiple lung primary nonsmall cell carcinomas from metastases. Am J Surg Pathol. 2009;33:1752–64.

    Article  PubMed  Google Scholar 

  81. D'Angelo SP, Park B, Azzoli CG, et al. Reflex testing of resected stage I through III lung adenocarcinomas for EGFR and KRAS mutation: report on initial experience and clinical utility at a single center. J Thorac Cardiovasc Surg. 2011;141:476–80.

    Article  PubMed  Google Scholar 

  82. Takamochi K, Oh S, Matsuoka J, et al. Clonality status of multifocal lung adenocarcinomas based on the mutation patterns of EGFR and K-ras. Lung Cancer. 2012;75:313–20.

    Article  PubMed  Google Scholar 

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Correspondence to Andre Luis Moreira M.D., Ph.D. .

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Moreira, A.L. (2015). Role of Immunohistochemistry in the Detection of Targetable Mutations. In: Moreira, A., Saqi, A. (eds) Diagnosing Non-small Cell Carcinoma in Small Biopsy and Cytology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1607-8_7

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