Prognostic significance of EGFR and Her-2 in oral cavity cancer in betel quid prevalent area

Abstract

Although several studies have found overexpression of epidermal growth factor receptor (EGFR) proteins EGFR and Her-2 in head and neck cancers, the clinical relevance of the finding varies. We examined the expression and clinical association of these molecules with oral squamous cell carcinoma in an area where betel chewing is prevalent. EGFR and Her-2 proteins were measured in 59 paired (grossly normal and cancer) tissues by an enzyme immunoassy method. The cutoff value for gene overexpression was defined as the level of mean expression in normal tissue plus two s.d. A total of 59% of the patients consumed alcohol, 90% smoked tobacco, and 90% chewed betel quid. Of the patients assayed, 34 (58%) and 24 (41%) had EGFR and Her-2 overexpression, with average 3.5-and 1.5-fold elevations. EGFR overexpression has been shown to be statistically associated with T stage, N stage, overall TMN stage, primary tumour depth, lymph node extra-capsular spread, and poor survival. Her-2 overexpression, however, did not demonstrate a similar association with clinicopathological parameters or therapeutic outcome. On multivariant analysis, EGFR overexpression (P ¼ 0.041) and N stage (P ¼ 0.024) were the only independent factors for overall survival. These results indicate that the molecular targeting therapy to EGFR may be a treatment for oral cavity cancer in the betel quid-chewing prevalent area.

Anti-HER-2 DNA vaccine protects Syrian hamsters against squamous cell carcinomas

“…This is probably the first demonstration of the efficacy of specific immunisation in the control of OSCC. Its significance is enhanced by the fact that a high percentage of OSCC overexpresses p185 receptors (Xia et al, 1999;Chen et al, 2003) and its extension, via a similar protocol, to another kind of cancer, of the evidence of the ability of DNA electroporation to evoke an efficient immune response to prevent mammary carcinoma in HER-2 transgenic mice (Quaglino et al, 2004a). Hamsters are naturally tolerant to the self-endogenous p185 protein and DNA electroporation overcame such tolerance.…”

“…Furthermore, it is a relatively low-cost technology that could also be afforded by developing countries, such as India, Bangladesh and Sri Lanka with their high incidence of OSCC and prevalence of HER-2-positive OSCC due to the consumption of betel quid (Chen et al, 2003). …”

“…Anticancer vaccines constitute a specific approach whose efficacy depends on how well the target tumour antigens are defined and whether there are conserved antigens shared by tumours of the same histotype in many individuals (Gilboa, 2004). The literature shows that HER-2 is one of the most common oncogenes overexpressed in OSCC (Chen et al, 2003). It encodes for a tyrosine-kinase receptor (p185) belonging to the family of epidermal growth factor receptors.…”

MIEN1 promotes oral cancer progression and implicates poor overall survival

“…3 Extensive research demonstrates the importance of various oncogenes and tumor suppressors along with associated signal transduction pathways in oral cancer progression. [5][6][7][8][9] It is evident that many of these pathways converge to facilitate invasion and migration of cells to the lymph nodes, characteristic of OSCC. Migration and invasion of cancer cells are hallmarks of cancer metastasis, 10,11 facilitated by processes including loss of cell adhesion and epithelial properties, cytoskeletal rearrangement, gain of mesenchymal form and ability to cleave the extracellular matrix by secreting proteases, and formation of new blood vessels by secreting angiogenic factors.…”

Overexpression of phosphorylated nuclear factor-kappa B in tonsillar squamous cell carcinoma and high-grade dysplasia is associated with poor prognosis

“…Enzyme immunoassay has revealed that EGFR overexpression in head and neck squamous cell carcinoma is found in 58% of cases and carries a statistical association with poor survival and TNM stage. 1 Immunohistochemical demonstration of EGFR overexpression in head and neck squamous cell carcinoma has been correlated with a high mitotic index and advanced (stage III and IV) tumors. 2 In a phase II clinical trial in refractory head and neck squamous cell carcinoma, ZD1839 (Iressa), targeted at EGFR, had single-agent activity with a 10.6% response rate and a disease control rate of 53% and was well tolerated.…”