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

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 ?2?1, ?3?1, ?6?1, and ?6?4 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 ?6, ?1, and ?4 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 ?6 expression at the tumor invasion front shared a significantly shortened relapse-free survival compared to patients with strong ?6 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 ?6 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 ?6?4 and ?6?1 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.

SUBMITTER: Vay C

PROVIDER: S-EPMC4232252 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Vay Christian C Hosch Stefan B SB Stoecklein Nikolas H NH Klein Christoph A CA Vallböhmer Daniel D Link Björn-Christian BC Yekebas Emre F EF Izbicki Jakob R JR Knoefel Wolfram T WT Scheunemann Peter P

PloS one 20141114 11

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 ...[more]

PMID: 25398092

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Project description:Purpose The development of esophageal squamous cell carcinoma (ESCC) is a complicated process in which cell adhesion and motility, mediated by integrins, are involved through connecting the cytoskeleton to extracellular matrix. Different mechanisms via which integrin ?6 participates in cancer invasion and metastasis have been described by numerous studies; however, the expression and clinical significance of integrin ?6 in ESCC remain unknown. Methods To investigate the differential expression of integrin ?6 in ESCC, qPCR and immunohistochemistry assays were performed in 10 paired human samples. A total of 137 ESCC samples were further enrolled to evaluate the expression levels of integrin ?6 and its endocytic trafficking regulator HS1-associated protein X-1 (HAX-1), followed by the evaluation of their correlation with clinicopathological parameters. The overall survival was analyzed using the Kaplan–Meier method, with significant variables further evaluated by multivariate Cox regression analyses. Results The expression of integrin ?6 was markedly increased in ESCC compared with matched adjacent normal tissues. Among the ESCC samples, positive expression of integrin ?6 was observed in 41.6% tumors, which was associated with histological differentiation, lymph node metastasis and TNM stage. High expression of HAX-1 was detected in 47.4% tumors, and there was a positive relationship between the expression levels of integrin ?6 and HAX-1. Furthermore, the expression of integrin ?6 and HAX-1 were independent unfavorable indicators for prognosis. Patients with positive integrin ?6 and high HAX-1 expression demonstrated worst outcomes. Conclusion The present findings suggested the predictive value of integrin ?6 and HAX-1 as independent indicators of poor prognosis for patients with ESCC, both of which may contribute to the tumor proliferation and metastasis, leading to ESCC progression. Therefore, combined targeting of integrin ?6 and HAX-1 may provide a potential novel approach for the treatment of ESCC.

Dataset Information

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

Publications

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

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