Integrin expression in esophageal squamous cell carcinoma

TY - JOUR

T1 - Integrin expression in esophageal squamous cell carcinoma

T2 - loss of the physiological integrin expression pattern correlates with disease progression

AU - Vay, Christian

AU - Hosch, Stefan B

AU - Stoecklein, Nikolas H

AU - Klein, Christoph A

AU - Vallböhmer, Daniel

AU - Link, Björn-Christian

AU - Yekebas, Emre F

AU - Izbicki, Jakob R

AU - Knoefel, Wolfram T

AU - Scheunemann, Peter

PY - 2014

Y1 - 2014

N2 - The integrins are a family of heterodimeric transmembrane signaling receptors that mediate the adhesive properties of epithelial cells affecting cell growth and differentiation. In many epithelial malignancies, altered integrin expression is associated with tumor progression and often correlates with unfavorable prognosis. However, only few studies have investigated the role of integrin expression in esophageal squamous cell carcinoma (ESCC). Using a novel quantifying immunofluorescence-staining assay, we investigated the expression of the integrins α2β1, α3β1, α6β1, and α6β4 in primary ESCC of 36 patients who underwent surgical resection. Magnitude and distribution of expression were analyzed in primary tumor samples and autologous esophageal squamous epithelium. The persistence of the physiologically polarized expression of the subunits α6, β1, and β4 in the tumor tissue was significantly associated with prolonged relapse-free survival (p = 0.028, p = 0.034, p = 0.006). In contrast, patients with reduced focal α6 expression at the tumor invasion front shared a significantly shortened relapse-free survival compared to patients with strong α6 expression at their stromal surfaces, as it was regularly observed in normal esophageal epithelium (p = 0.001). Multivariate regression analysis identified the maintenance of strong α6 immunoreactivity at the invasion front as an independent prognostic factor for increased relapse-free and disease-specific survival (p = 0.003; p = 0.003). Our findings suggest that alterations in both pattern and magnitude of integrin expression may play a major role in the disease progression of ESCC patients. Particularly, the distinct expression of the integrins α6β4 and α6β1 at the invasion front as well as the maintenance of a polarized integrin expression pattern in the tumor tissue may serve as valuable new markers to assess the aggressiveness of ESCC.

AB - The integrins are a family of heterodimeric transmembrane signaling receptors that mediate the adhesive properties of epithelial cells affecting cell growth and differentiation. In many epithelial malignancies, altered integrin expression is associated with tumor progression and often correlates with unfavorable prognosis. However, only few studies have investigated the role of integrin expression in esophageal squamous cell carcinoma (ESCC). Using a novel quantifying immunofluorescence-staining assay, we investigated the expression of the integrins α2β1, α3β1, α6β1, and α6β4 in primary ESCC of 36 patients who underwent surgical resection. Magnitude and distribution of expression were analyzed in primary tumor samples and autologous esophageal squamous epithelium. The persistence of the physiologically polarized expression of the subunits α6, β1, and β4 in the tumor tissue was significantly associated with prolonged relapse-free survival (p = 0.028, p = 0.034, p = 0.006). In contrast, patients with reduced focal α6 expression at the tumor invasion front shared a significantly shortened relapse-free survival compared to patients with strong α6 expression at their stromal surfaces, as it was regularly observed in normal esophageal epithelium (p = 0.001). Multivariate regression analysis identified the maintenance of strong α6 immunoreactivity at the invasion front as an independent prognostic factor for increased relapse-free and disease-specific survival (p = 0.003; p = 0.003). Our findings suggest that alterations in both pattern and magnitude of integrin expression may play a major role in the disease progression of ESCC patients. Particularly, the distinct expression of the integrins α6β4 and α6β1 at the invasion front as well as the maintenance of a polarized integrin expression pattern in the tumor tissue may serve as valuable new markers to assess the aggressiveness of ESCC.

KW - Carcinoma, Squamous Cell

KW - Cluster Analysis

KW - Disease Progression

KW - Disease-Free Survival

KW - Epithelium

KW - Esophageal Neoplasms

KW - Fluorescent Antibody Technique

KW - Humans

KW - Integrins

KW - Kaplan-Meier Estimate

KW - Multivariate Analysis

KW - Neoplasm Invasiveness

KW - Protein Subunits

KW - Recurrence

KW - Journal Article

U2 - 10.1371/journal.pone.0109026

DO - 10.1371/journal.pone.0109026

M3 - SCORING: Journal article

C2 - 25398092

VL - 9

SP - e109026

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 11

ER -