EGFR (HER) family protein expression and cytogenetics in 219 squamous cell carcinomas of the upper respiratory tract: ERBB2 overexpression independent prediction of poor prognosis.

Objective: To retrospectively evaluate the prognostic impact of gene status and protein expression of receptor tyrosine kinases of the HER (human epidermal growth factor receptor related) family in relation to established clinicopathologic parameters in squamous cell carcinomas of the upper respiratory tract.

Study Design: Immunohistochemistry and fluorescence in situ hybridization for HER1-4 and the proliferation marker Ki-67 was performed in 219 cases of head and neck squamous cell carcinomas and related to long-term clinical follow-up. Additionally, the prognostic impact of chromosomal instability was analyzed.

Results: High expression of HER1 and HER2 was present in 49.4% and 6.6% of tumors, respectively. Expression of HER3 and HER4 appeared negative or inconspicuous. A gene amplification of HER1 occurred in 5.2% of tumors, whereas none of the tumors showed an amplification of HER2-4 loci. In univariate overall survival analysis a negative prognostic impact could be demonstrated for high expression of HER2 (p < 0.01), advanced local tumor growth (p < 0.01), lymph node metastasis (p < 0.01), presence of residual tumor after surgical therapy (p < 0.01), high proliferative activity (Ki-67; p = 0.02) and high chromosomal instability (p = 0.01). According to the multivariate analysis, the strongest negative predictors of survival were advanced tumor growth (p < 0.01), presence of residual tumor (p < 0.01), high expression of HER2 (p < 0.01) and chromosomal instability (p = 0.03).

Conclusion: Overexpression of HER2 and presence of chromosomal instability harbor an additional prognostic impact on disease-specific survival and prove to be independent negative prognostic factors in head and neck squamous cell carcinomas.