PMID- 28854970 OWN - NLM STAT- MEDLINE DCOM- 20180503 LR - 20181202 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 17 IP - 1 DP - 2017 Aug 30 TI - EGFR copy number alterations in primary tumors, metastatic lymph nodes, and recurrent and multiple primary tumors in oral cavity squamous cell carcinoma. PG - 592 LID - 10.1186/s12885-017-3586-9 [doi] LID - 592 AB - BACKGROUND: The EGFR and downstream signaling pathways play an important role in tumorigenesis in oral squamous cell carcinoma (OSCC). Gene copy number alteration is one mechanism for overexpressing the EGFR protein and was also demonstrated to be related to lymph node metastasis, tumor invasiveness and perineural invasion. Therefore, we hypothesized that EGFR gene copy number alteration in the primary tumor could predict amplification in recurrent tumors, lymph node metastatic foci or secondary primary tumors. METHODS: We recruited a group of newly diagnosed OSCC patients (n = 170) between Mar 1997 and Jul 2004. Metastatic lymph nodes were identified from neck dissection specimens (n = 57). During follow-up, recurrent lesions (n = 41) and secondary primary tumors (SPTs, n = 17) were identified and biopsied. The EGFR gene amplifications were evaluated by fluorescence in situ hybridization (FISH) assay in primary tumors, metastatic lymph nodes, recurrences and SPTs. RESULTS: Of the 170 primary OSCCs, FISH showed low EGFR amplification/polysomy in 19 (11.4%) patients and amplification in 33 (19.8%) patients. EGFR gene amplification was related to lymph node metastasis (chi2 trend test: p = 0.018). Of 57 metastatic lymph nodes, nine (15.8%) had EGFR polysomy and 14 (24.6%) had EGFR gene amplification. The concordance rate of EGFR gene copy number in primary tumors and lymph node metastasis was 68.4% (McNemar test: p = 0.389). Of 41 recurrent tumors, five (12.2%) had EGFR polysomy and five (12.2%) had gene amplification. The concordance rate of EGFR gene copy number between primary tumors and recurring tumors was 65.9% (McNemar test: p = 0.510). The concordance rate between primary tumors and SPTs was 70.6%. EGFR amplification in either primary tumors, metastatic lymph nodes or recurrent tumors had no influence on patient survival. CONCLUSION: We can predict two-thirds of the EGFR gene copy number alterations in lymph node metastasis or recurrent tumors from the analysis of primary tumors. For OSCC patients who are unable to provide lymph node or recurrent tumor samples for EGFR gene copy number analysis, examining primary tumors could provide EGFR clonal information in metastatic, recurrent or SPT lesions. FAU - Huang, Shiang-Fu AU - Huang SF AUID- ORCID: 0000-0003-3582-9938 AD - Department of Otolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, No. 5 Fu-Shin Street, Kwei-Shan, Taoyuan, Taiwan. shiangfu.huang@gmail.com. AD - Department of Public Health, Chang Gung University, Tao-Yuan, Taiwan. shiangfu.huang@gmail.com. AD - Taipei CGMH Head and Neck Oncology Group, Tao-Yuan, Taiwan. shiangfu.huang@gmail.com. FAU - Chien, Huei-Tzu AU - Chien HT AD - Department of Public Health, Chang Gung University, Tao-Yuan, Taiwan. AD - Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan. FAU - Cheng, Sou-De AU - Cheng SD AD - Department of Anatomy, Chang Gung University, Tao-Yuan, Taiwan. FAU - Chuang, Wen-Yu AU - Chuang WY AD - Department of Pathology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan. FAU - Liao, Chun-Ta AU - Liao CT AD - Department of Otolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, No. 5 Fu-Shin Street, Kwei-Shan, Taoyuan, Taiwan. AD - Taipei CGMH Head and Neck Oncology Group, Tao-Yuan, Taiwan. FAU - Wang, Hung-Ming AU - Wang HM AD - Taipei CGMH Head and Neck Oncology Group, Tao-Yuan, Taiwan. AD - Division of Hematology/Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan. LA - eng PT - Journal Article DEP - 20170830 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Adult MH - Aged MH - Carcinoma, Squamous Cell/*genetics MH - DNA Copy Number Variations/*genetics MH - ErbB Receptors/*genetics MH - Gene Amplification/genetics MH - Gene Dosage/genetics MH - Genes, erbB-1/*genetics MH - Humans MH - Lymphatic Metastasis/*genetics MH - Middle Aged MH - Mouth Neoplasms/*genetics MH - Neoplasm Recurrence, Local/genetics MH - Neoplasms, Multiple Primary/*genetics PMC - PMC5576106 OTO - NOTNLM OT - Epidermal growth factor receptor (EGFR) OT - Gene amplification OT - Multiple primary tumors, fluorescence in situ hybridization OT - Oral cavity squamous cell carcinoma OT - Recurrence, metastasis COIS- COMPETING INTEREST: The authors declare that they have no competing interests. ETHICS APPROVAL AND CONSENT TO PARTICIPATE: All patients signed informed consent for participation of this study. This study had ethics approval and consent by the ethic committee in Chang Gung Memorial Hospital (Institutional Review Board of Chang Gung Medical Foundation, IRB No. 97-1593A3), Taiwan, R.O.C.. CONSENT FOR PUBLICATION: Not applicable. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2017/09/01 06:00 MHDA- 2018/05/04 06:00 PMCR- 2017/08/30 CRDT- 2017/09/01 06:00 PHST- 2017/01/23 00:00 [received] PHST- 2017/08/22 00:00 [accepted] PHST- 2017/09/01 06:00 [entrez] PHST- 2017/09/01 06:00 [pubmed] PHST- 2018/05/04 06:00 [medline] PHST- 2017/08/30 00:00 [pmc-release] AID - 10.1186/s12885-017-3586-9 [pii] AID - 3586 [pii] AID - 10.1186/s12885-017-3586-9 [doi] PST - epublish SO - BMC Cancer. 2017 Aug 30;17(1):592. doi: 10.1186/s12885-017-3586-9.