Associations Of Fibronectin And Laminin Overexpression With Tumor Microvessels Density And Myofibroblasts Amount In Esophageal Squamous Cell Carcinoma And Their Clinical Significances

Objective Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive kinds of digestive tract tumor, the disease control rate and patients prognosis were still severe even with improvement of comprehensive treatments. Metastasis of lymph nodes and distant organs occurred in more than 85% patients within five years. Intensified researches about mechanisms of tumor invasion and metastasis would be regarded as crux of prognostic amelioration in ESCC patients. Non-collagenous extracellular matrix fibronectin (FN) and laminin (LN) located on the epithelial basement membranes were deemed to prevent tumor cells from invading interstitial substance. Whereas emerging evidences bring to our attention in the process their crucial roles of promoting evolution in several tumors. ESCC was observed to be with enrichment of mesenchyme, in which angiogenesis provides nutritional support and enabling environment for growth, invasion and metastasis of ESCC cells, and myofibroblasts (MFs) as dominant component were reported to promote tumor progression by participating in immune protection and intratumoral microenvironment remodeling. We aimed to investigate the associations of FN and LN overexpressed in ESCC tissue with the densities of tumor microvessels and stromal myofibroblasts, and evaluate the significance and applied value of FN and LN overexpression as diagnostic and therapeutic targets through analysing their influences upon tumor malignant properties and patients prognosis.Methods Immunohistochemistry was performed to detect the levels of FN and LN expression in the tumor and paracarcinomatous tissues and the densities of microvessels and stromal myofibroblasts visibly marked by CD34 and a-smooth muscle actin (a-SMA) from 53 ESCC specimens. The relationships between them were performed by Spearman’s rank correlation test. Whether there existed statistical discrepancies between outcomes of patients with poor and strong expression patterns of FN and LN was determined by Kaplan-Meier analysis and log-rank test. The Cox regression model was used for multivariate survival analysis.Results The FN and LN expression in ESCC tissues were abnormally abundant compared with paracarcinomatous tissues. Positive rate of FN in the ESCC tissues was 96.2%(X2=17.162, P=0.000), and 52.8% (X2=23.277, P=0.000) of the ESCC tissue specimens expressed LN. The increased FN and LN were proportionate to high microvessels density (MVD) (FN:P=0.008; LN:P=0.039) and plentiful stromal myofibroblasts (FN:P=0.016; LN:P=0.023), as well as associated with TNM stage (FN:P=0.000; LN:P=0.004) and venous invasion (FN:P=0.002; LN:P=0.011) intimately. Overall survival (OS) rate decreased in the patients with strongly positive expressed pattern (FN:P=0.005; LN:P=0.004). Statistical difference between disease free survival (DFS) rates of the two groups of patients was found into neither FN nor LN expressed pattern. Multivariate survival analysis by the Cox regression model indicated that the FN (P=0.201) and LN (P=0.142) overexpression in ESCC tissue could not predict patients overall survival independently.Conclusion Overexpressions of FN and LN in the ESCC tissue which related to remodeling of mesenchymal components and structure may affect tumor progression and patients prognosis to an extent through establishing a permissive environment for tumor invasion and metastasis.