Get access

Immunohistochemical expression patterns of the HER4 receptors in normal mucosa and in laryngeal squamous cell carcinomas: Antioncogenic significance of the HER4 protein in laryngeal squamous cell carcinoma


  • This work was supported in part by grant D.1.-2006 from the Catholic University of the Sacred Heart within its program of promotion and diffusion of scientific research. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

  • Francesco Bussu and Franco O. Ranelletti contributed equally to this work.



The prognosis for laryngeal squamous cell carcinoma (LSCC) has not shown any improvement in the last 30 years because of inadequate prognostic stratification. Therefore, the detection of reliable molecular markers may have a significant impact on clinical practice. As promising data regarding HER1/EGFR have been published, the purpose of the present study was to elucidate the role of the other receptors of the HER family.

Study Design:



We used quantitative immunohistochemistry to evaluate the expression pattern of the HER4 receptors cytokeratin (CK)-14, CK-17, and proliferating cell nuclear antigen in 67 LSCCs and assessed correlations with various prognostic parameters.


HER1 levels inversely correlated with those of HER2–4. The negative prognostic value of HER1 was confirmed, and a protective role for HER2–4 was found. Specifically, the overexpression of HER4 and its nuclear localization are protective and are associated with a better prognosis.


Semiquantitative evaluation of HER2–4 provides predictive information that can be combined with HER1 expression data for molecular characterization of LSCC. The pattern of localization of HER4 is an easily evaluable qualitative parameter with a clear correlation with prognosis. The immunohistochemical methods described in this article are reliable, reproducible, and potentially translatable to clinical practice. Laryngoscope, 2012