Zekiye AYDOĞDU, Sait TÜMER, Aydanur KARGI, Sebnem YİLDİRİMCAN KADİCESME, Cigdem Eresen YAZİCİOGLU, Oğuz ALTUNGÖZ

HER-2/neu alterations in non-small cell lung cancer: A comprehensive evaluation by fluorescence in situ hybridization and immunohistochemistry

Aim: The molecular relationships of protein overexpression and HER-2/neu gene amplification in lung cancers are not clearlydefined. The aim of the study is to evaluate HER-2/neu changes in non-small cell lung cancer with in situ hybridization andimmunohistochemistry, to compare the effectiveness of both methods and to examine the influence of HER-2/neu gene and proteinlevel alterations on prognosis.Material and Methods: HER-2/neu alterations were analyzed with fluorescence in situ hybridization and immunohistochemistry in24 patients with non-small cell lung cancer.Results: Of 24 patients, 13 (54%) were found immunohistochemistry (IHC) positive, on the other hand 24 (100%) were foundfluorescence in situ hybridization (FISH) negative. Balanced trisomy was detected in 23 out of FISH negative cases and balancedquadrisomy was detected in one case. Our study has revealed that overexpression of HER-2/neu protein is not associated with realgene amplification. No significant correlation was detected between HER-2/neu overexpression with amplification, and prognosisof non-small cell lung cancer.Conclusion: No correlation is present between fluorescence in situ hybridization and immunohistochemistry results. HER-2/neualterations are present in non-small cell lung cancers. Therefore, HER-2/neu overexpression may be associated with transcriptionalmechanisms rather than gene amplification.

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1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7-30.
2. Wang D, Pham NA, Tong J, et al. Molecular heterogeneity of non-small cell lung carcinoma patient-derived xenografts closely reflect their primary tumors. Int J Cancer 2017;140:662-73.
3. Sasaki H, Suzuki A, Tatematsu T, et al. Prognosis of recurrent non-small cell lung cancer following complete resection. Oncol Lett 2014;7:1300-4.
4. Iqbal N, Iqbal N, et al. Human epidermal growth factor receptor 2 (HER2) in Cancers: overexpression and therapeutic lmplications. Mol Biol Int 2014;2014:1-9.
5. Roskoski R. The ErbB/HER family of protein-tyrosine kinases and cancer. Pharmacol Res 2014;79:34-74.
6. Kobyakov DS, Avdalyan AM, Bobrov IP, et al. Correlation of HER-2/ Neu protein expression and HER2 gene amplification with clinical morphological parameters of nonsmall cell lung cancer. Bull Exp Biol Med 2014;157:789-93.
7. Rothschild SI. Targeted therapies in non-small cell lung cancer—beyond EGFR and ALK. Cancers (Basel) 2015;7:930- 49.
8. Liu L, Shao X, Gao W, et al. The role of human epidermal growth factor receptor 2 as a prognostic factor in lung cancer: A meta-analysis of published data. J Thorac Oncol 2010;5:1922-32.
9. Rosell R. Toward customized trastuzumab in HER-2/neuoverexpressing non-small-cell lung cancers. J Clin Oncol 2004;22:1171-3.
10. Barok M, Joensuu H, Isola J. Trastuzumab emtansine: mechanisms of action and drug resistance. Breast Cancer Res 2014;16:R22.
11. Ohashi K, Hotta K, Hirata T, et al. Trastuzumab Emtansine in HER2+ Recurrent Metastatic Non–Small-Cell Lung Cancer: Study Protocol. Clin Lung Cancer 2017;18:92-5.
12. Ozer O, Sahin FI, Aydemir F, et al. HER-2 / neu gene amplification in paraffin- embedded tissue sections of meningioma patients meningiom olgular › na ait parafin blok doku kesitlerinde her2 /neu. Turk Neurosurg 2009;19:135-8.
13. Amplification G, Immunohistochemistry W, Ciampa A, et al. HER-2 status in breast cancer. Appl Immunohistochem 2006;14:132-7.
14. Meert AP, Martin B, Verdebout JM, et al. Is there a relationship between c-erbB-1 and c-erbB-2 amplification and protein overexpression in NSCLC? Lung Cancer 2005;47:325-36.
15. Pellegrini C, Falleni M, Marchetti A, et al. HER-2 / Neu alterations in non-small cell lung cancer : a comprehensive evaluation by real time reverse transcription-pcr, Fluorescence in Situ hybridization, and immunohistochemistry. Clin Cancer Res 2003;9:3645-52.
16. Tissue T, Winston J, Wiseman S, et al. HER-2 / neu protein expression and gene alteration in stage ı-ıııa non – smallcell lung cancer : a study of 140 cases using a combination. Cancer 2003;12:201-11.
17. Cox G, Vyberg M, Melgaard B, et al. HER2 expression and gene amplification in non-small cell lung cancer 2001;15:480-3.
18. Nakamura H, Saji H, Ogata A, et al. Correlation between encoded protein overexpression and copy number of the HER2 gene with survival in non-small cell lung cancer. Int J Cancer 2003;103:61-6.
19. Bunn PA, Helfrich B, Soriano AF, et al. Expression of Her-2/neu in human lung cancer cell lines by immunohistochemistryand fluorescence in situ hybridization and its relationship to in vitro cytotoxicity by trastuzumab and chemotherapeutic agents. Expression of Her-2/neu in human lung cancer cell lines by immunohistochemistryand fluorescence in situ hybridization and its relationship to in vitro cytotoxicity by trastuzumab and chemotherapeutic agents. Clin Cance 2001;7:3239-50.
20. Hicks DG, Tubbs RR. Assessment of the HER2 status in breast cancer by fluorescence in situ hybridization: a technical review with interpretive guidelines. Hum Pathol 2005;36:250-61.
21. Horton J. Trastuzumab use in breast cancer: clinical issues. Cancer Control 2002;9:499-507.
22. Cuadros M, Talavera P, López FJ, et al. Real-time RT-PCR analysis for evaluating the Her2/neu status in breast cancer. Pathobiology 2010;77:38-45.
23. Barberis M, Pellegrini C, Cannone M, Quantitative PCR and HER2 testing in breast cancer: A technical and costeffectiveness analysis. Am J Clin Pathol 2008;129:563-70.
24. Homaei Shandiz F, Fani A, Shakeri S, et al. Fluorescent in situ hybridization and real-time quantitative polymerase chain reaction to evaluate HER-2/neu status in breast cancer. Iran J Pathol 2017;12:67-73.
25. Park S, Wang HY, Kim S, et al. Quantitative RT-PCR assay of HER2 mRNA expression in formalin-fixed and paraffinembedded breast cancer tissues. Int J Clin Exp Pathol 2014;7:6752-9.
26. Yoshizawa A, Sumiyoshi S, Sonobe M, et al. HER2 status in lung adenocarcinoma: A comparison of immunohistochemistry, fluorescence in situ hybridization (FISH), dual-ISH, and gene mutations. Lung Cancer 2014;85:373-8.