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

Abstract

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 (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. 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.

Secreted amphiregulin promotes vincristine resistance in oral squamous cell carcinoma

“…In Taiwan, oral cancer accounts for the fourth highest incidence of malignancy in males (55). Numerous studies indicate that EGFR is frequently overexpressed in human OSCC (56)(57)(58)(59).…”

“…High EGFR expression has been associated with resistance to chemotherapeutic agents used in the treatment of OSCC, including cisplatin, 5-FU, cyclophosphamide and doxorubicin, suggesting that EGFR signaling may be a promising target for OSCC therapy (58)(59)(60). Cetuximab is a chimeric IgG1-human antibody targeted against the extracellular domain of EGFR (61).…”

Cancer: the dark side of wound healing

“…EGFR amplification, overexpression and gain‐of‐function mutations are highly prevalent in cutaneous and head and neck SCCs (cSCC & HNSCC) . In cancer tissues, EGFR expression status is positively correlated with lymph node involvement, tumour grade and stage . Recently, EGF has been shown to induce EMT and confer stem cell‐like properties to oral cancer cells through the ‘Warburg effect’ .…”

Immunohistochemical Expression of Epidermal Growth Factor Receptor among Metastatic and Nonmetastatic Oral Squamous Cell Carcinomas

“…18 The deregulation of EGFR molecule results in the net effect of TGF-β signalling accompanied by a concomitant EMT-associated gene switch of tumor cells, as well as gaining of a migratory mesenchymal phenotype. 19,20 TGFα-EGFR signalling in colon cancer cells creates a microenvironment that is favorable for metastasis, providing a justification for efforts to inhibit EGFR signalling in TGFα-positive cancers. These EGFR aberrations deregulate downstream pro-oncogenic signalling pathways, including the RAS-RAF-MEK-ERK MAPK and AKT-PI3K-mTOR pathways.…”