Integrinexpression beim Plattenepithelkarzinom des Ösophagus: Vergleichende Untersuchung zur Expression der Integrin-Untereinheiten α2, α3, α6, β1 und β4 in Primärtumoren und Ösophagusmukosa Integrin expression in esophageal squamous cell carcinoma: differential expression of integrin subunits α2, α3, α6, β1 and β4 in primary lesions and non-malignant esophageal epithelium

The integrins, a family of heterodimeric transmembrane receptor proteins, mediate cell-to-cell and cell-to-extracellular matrix (ECM) adhesive interactions and transduce signals from the ECM to the cell interior. Their contributions to tissue integrity and cell migration as well as their influence on cell growth and differentiation imply a role for integrins in tumour progression and metastasis. Solid tumours frequently present with altered integrin expression patterns and often prognosis is related to aberrant expression. However, until now little is known about the integrin expression in esophageal squamous cell carcinoma (ESCC). We therefore investigated the expression of integrin subunits α2, α3, α6, β1, and β4 in 36 patients with ESCC using an immunofluorescence staining assay. Quantity and distribution of integrin expression in tumor samples were analyzed and compared to integrin expression in normal corresponding esophageal mucosa. In normal esophageal epithelium α6 and β4 expression was notably strengthened along the basement membrane. A similar expression pattern was observed in more than 90 % of the tumor samples, where α6 and β4 were predominantly expressed at the invasive tumor front. Thereby, patients with reduced focal α6 expression had a significantly reduced relapse-free survival compared to patients with strong α6 expression (p < 0.005). Furthermore, strong β1 expression at the tumor invasion front was associated with absence of lymph node metastasis (pN0) (p < 0.02). In addition, patients whose primary tumors maintained a polarized integrin expression as observed in normal esophageal mucosa tended towards a favourable prognosis compared to patients with aberrant integrin expression patterns. Polarized expression of the integrin subunits α6 and β4 was significantly associated with a prolonged relapse-free survival (p < 0.05). However, only strong focal α6 expression could be confirmed as an independent prognostic factor for an increased relapse-free survival in the multivariate analysis. In conclusion, these findings are consistent with the hypothesis that in squamous cell carcinoma both alterations in pattern and quantity of integrin expression may affect disease progression and patient survival. The focal expression of integrin α6β4 at the invasive tumor front may represent an additional factor to assess the aggressiveness of ESCC.