title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Retrospective.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otolaryngology, Catholic University of the Sacred Heart, Rome. francescobussu@yahoo.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Bussu
authors.forename: Franco O
authors.initials: FO
authors.lastname: Ranelletti
authors.forename: Marco
authors.initials: M
authors.lastname: Gessi
authors.forename: Cristina
authors.initials: C
authors.lastname: Graziani
authors.forename: Paola
authors.initials: P
authors.lastname: Lanza
authors.forename: Libero
authors.initials: L
authors.lastname: Lauriola
authors.forename: Gaetano
authors.initials: G
authors.lastname: Paludetti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Almadori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000628:therapy; D059186:Chemoradiotherapy, Adjuvant; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007124:Immunoenzyme Techniques; D053547:Keratin-14 / Q000032:analysis; D053537:Keratin-17 / Q000032:analysis; D007820:Laryngeal Mucosa / Q000473:pathology; D007822:Laryngeal Neoplasms / Q000473:pathology* / Q000628:therapy; D007825:Laryngectomy; D007830:Larynx / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D037981:Neck Dissection; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D066247:Receptor, ErbB-4; D012680:Sensitivity and Specificity; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D053547:Keratin-14; D053537:Keratin-17; D018809:Proliferating Cell Nuclear Antigen; C512478:EGFR protein, human; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4