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Integrin expression in esophageal squamous cell carcinoma: loss of the physiological integrin expression pattern correlates with disease progression.

Vay C, Hosch SB, Stoecklein NH, Klein CA, Vallböhmer D, Link BC, Yekebas EF, Izbicki JR, Knoefel WT, Scheunemann P - PLoS ONE (2014)

Bottom Line: In many epithelial malignancies, altered integrin expression is associated with tumor progression and often correlates with unfavorable prognosis.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery (A), Heinrich-Heine-University and University Hospital Düsseldorf, Düsseldorf, Germany; Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

ABSTRACT
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.

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Immunofluorescence staining patterns of the integrin subunits α2, α3, α6, β1, and β4 in tissue sections of normal esophageal squamous epithelium and esophageal squamous cell carcinoma (ESCC).Magnification 100 fold. Enhanced staining intensities at the basal surface of the epithelium and at the tumor invasion front are marked by an arrow (↑).
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pone-0109026-g002: Immunofluorescence staining patterns of the integrin subunits α2, α3, α6, β1, and β4 in tissue sections of normal esophageal squamous epithelium and esophageal squamous cell carcinoma (ESCC).Magnification 100 fold. Enhanced staining intensities at the basal surface of the epithelium and at the tumor invasion front are marked by an arrow (↑).

Mentions: In all cases with an enhanced integrin expression at the tumor invasion front, the staining intensities were measurably increased in comparison to the marginal and central tumor areas (Fig. 2 and Table 2). This distinct amplification of expression was observed for the α6 and the β4 subunit in 97% (35/36) and 94% (32/43) of the tumors, respectively. In contrast, a clearly enhanced α2, α3, and β1 expression at the tumor invasion front was observed in only 8% (3/36), 25% (9/36), and 30% (9/30) of the tumors, respectively.


Integrin expression in esophageal squamous cell carcinoma: loss of the physiological integrin expression pattern correlates with disease progression.

Vay C, Hosch SB, Stoecklein NH, Klein CA, Vallböhmer D, Link BC, Yekebas EF, Izbicki JR, Knoefel WT, Scheunemann P - PLoS ONE (2014)

Immunofluorescence staining patterns of the integrin subunits α2, α3, α6, β1, and β4 in tissue sections of normal esophageal squamous epithelium and esophageal squamous cell carcinoma (ESCC).Magnification 100 fold. Enhanced staining intensities at the basal surface of the epithelium and at the tumor invasion front are marked by an arrow (↑).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232252&req=5

pone-0109026-g002: Immunofluorescence staining patterns of the integrin subunits α2, α3, α6, β1, and β4 in tissue sections of normal esophageal squamous epithelium and esophageal squamous cell carcinoma (ESCC).Magnification 100 fold. Enhanced staining intensities at the basal surface of the epithelium and at the tumor invasion front are marked by an arrow (↑).
Mentions: In all cases with an enhanced integrin expression at the tumor invasion front, the staining intensities were measurably increased in comparison to the marginal and central tumor areas (Fig. 2 and Table 2). This distinct amplification of expression was observed for the α6 and the β4 subunit in 97% (35/36) and 94% (32/43) of the tumors, respectively. In contrast, a clearly enhanced α2, α3, and β1 expression at the tumor invasion front was observed in only 8% (3/36), 25% (9/36), and 30% (9/30) of the tumors, respectively.

Bottom Line: In many epithelial malignancies, altered integrin expression is associated with tumor progression and often correlates with unfavorable prognosis.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery (A), Heinrich-Heine-University and University Hospital Düsseldorf, Düsseldorf, Germany; Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus