title: Parameters of Stromal Activation and Epithelial to Mesenchymal Transition as Predictive Biomarkers for Induction Chemotherapy in Patients With Locally Advanced Oral Cavity and Oropharyngeal Squamous Cell Cancer.
abstract: OBJECTIVE
  Induction chemotherapy (IC) is likely to be effective for biologically distinct subgroups of oral cancer and biomarker development may lead to identification of those patients.
  
  
  METHODS
  We evaluated immune cell infiltration, stroma formation and structure of the invasive front as well as the immunohistochemical expression of alpha smooth muscle actin (ASMA), CD163, E-cadherin, N-cadherin, and the laminin gamma 2 chain in pretreatment biopsy specimens and surgical resections after IC in 20 patients with locally advanced oral cancer who were treated in a prospective, ongoing, phase II trial on IC using docetaxel, cisplatin, and 5-fluorouracil (TPF).
  
  
  RESULTS
  Significant negative prognostic factors for incomplete pathological tumor response to IC were alcohol abuse (P=0.032), cN+ (P=0.042), and <30% tumor reduction after first cycle of IC (P=0.034). Of the investigated histological parameters and biomarkers only a low membrane-bound expression of E-cadherin showed a trend to be associated with incomplete response to IC (P=0.061). Low expression of ASMA in stromal vessels and a strong tumor invasion front were significantly associated to tumor recurrence (P=0.024 andP=0.004, respectively). The median follow-up of all patients was 35 months. Alcohol abuse (P<0.001), <30% tumor reduction after first cycle of IC (P=0.005), and a strong tumor invasion front (P=0.019) were negative prognostic factors for overall survival.
  
  
  CONCLUSIONS
  A strong predictive biomarker among the investigated parameters for benefitting from TPF IC could not be found. The extent of the tumor invasion front was a negative prognostic marker for recurrence and survival in oral cancer treated by TPF IC followed by surgery and postoperative radiochemotherapy.
authors.affiliation: Institute of Pathology, Jena University Hospital, Jena, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Geweiler
authors.affiliation: Department of Otorhinolaryngology, Jena University Hospital, Jena, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Inhestern
authors.affiliation: Institute of Pathology, Jena University Hospital, Jena, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Berndt
authors.affiliation: Department of Otorhinolaryngology, Jena University Hospital, Jena, Germany.
authors.forename: Orlando
authors.initials: O
authors.lastname: Guntinas-Lichius
keywords: Docetaxel; Induction Chemotherapy; Mouth Neoplasms; Neoplasm Invasiveness; Survival