EGFR copy number alterations in primary tumors, metastatic lymph nodes, and recurrent and multiple primary tumors in oral cavity squamous cell carcinoma

Shiang-Fu Huang,Wen-Yu Chuang,Hung-Ming Wang,Huei-Tzu Chien,Sou-De Cheng,Chun-Ta Liao

doi:10.1186/s12885-017-3586-9

Abstract

BackgroundThe 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.MethodsWe 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.ResultsOf 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 (χ2 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.ConclusionWe 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.

Highlights

The Epidermal growth factor receptor (EGFR) and downstream signaling pathways play an important role in tumorigenesis in oral squamous cell carcinoma (OSCC)
We previously demonstrated that lymph node metastasis, tumor cell differentiation and perineural invasion and tumor stage are correlated with EGFR gene amplification [7]
It is worthwhile to investigate tumor cells with increased EGFR amplification because the number of EGFR copies plays an important role in metastasis, recurrence or development of secondary primary tumors (SPTs)

Summary

Introduction

The EGFR and downstream signaling pathways play an important role in tumorigenesis in oral squamous cell carcinoma (OSCC). The primary treatment for oral cavity squamous cell carcinoma (OSCC) is radical surgery with or without post-operative adjuvant radio−/chemotherapy and this treatment approach can result in good loco-regional control [3]. We previously demonstrated that lymph node metastasis, tumor cell differentiation and perineural invasion and tumor stage are correlated with EGFR gene amplification [7]. Those previous findings indicate that tumor cells with EGFR amplification are invasive. It is worthwhile to investigate tumor cells with increased EGFR amplification because the number of EGFR copies plays an important role in metastasis, recurrence or development of secondary primary tumors (SPTs)

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Discussion

Conclusion