Integrin expression in esophageal squamous cell carcinoma
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Integrin expression in esophageal squamous cell carcinoma : loss of the physiological integrin expression pattern correlates with disease progression. / Vay, Christian; Hosch, Stefan B; Stoecklein, Nikolas H; Klein, Christoph A; Vallböhmer, Daniel; Link, Björn-Christian; Yekebas, Emre F; Izbicki, Jakob R; Knoefel, Wolfram T; Scheunemann, Peter.
In: PLOS ONE, Vol. 9, No. 11, 2014, p. e109026.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -