E-cadherin And PCNA Expression And Their Clinicopaththological Significance In Hunman Non-small Cellule Lung Cancer

Background and Objective: Non-small cellule lung cancers(NSCLCs) is the most common type of lung cancer. Among them, majority are squamous cell carcinomas and adenocarcinomas. In lung cancer, metastasis can occur at very early stage and it is the main reason causing failure of clinical treatment and patients death. Hence, right evaluation of the lung cancer biological behaviors plays an important role in guiding the clinic diagnosis and treatment. Tumor's metastasis is a complex process which involves multisteps, mainly including tumor cells shatter from the primary tumor; break down extracellular matrix and basement membrane; invade the blood vessel or lymph vessel into stream; then migrate out of vessel then form metastatic tumor. During this process, the key step is tumor cells shattering from the primary tumor. By recent studies, E-cadherin has been found to be associated with this step of metastasis of cancer. E-cadherin(epithelial cadherin , E-cad)is one of the major calcium-dependent cell adhesion molecules playing a major role in the maintenance of intercellular junctions in normal epithelial cells. The expression of E-cadherin has been found to be down-regulated in many human digestive system cancers, suggesting that E-cadherin down regulation may play a role in tumor progression and metastasis. However, in NSCLCs, its importance has not yet been sufficiently investigated; especially the relationship between E-cad expression and clinical pathological factors of NSCLCs is still controversial topic. This study isdesigned to determine relationship between the expression of E-cad and histological type of NSCLC, differentiation as well as metastasis. Furthermore, combination detection of the expression of PCNA (proliferating cell nuclear antigen) and E-cad was used to explore the possible molecular mechanism of E-cad affecting NSCLCs differentiation and metastasis.Methods: 34 primary NSCLCs cases underwent surgical resection at affiliated hospital of Dalian university between 2004 and 2006. Immunohistochemical and immunofluorescence double staining were performed to examine the expression of E-cad and PCNA. The evaluation of these expressions was determined as sumdensity by microscope image analysis system. For statistical analysis, Spearman rank correlation analysis and independent t test were used to analyze the relationship between expression of these two proteins and pathological factors.Results: The mean expression values of E-cad in squamous cell carcinomas ( 138.4±18.9) and that in adenocarcinomas(179.0±30.3) has no significant difference(p=0.33). However, the expression value of E-cad has positive correlation with histological differentiation grade(r= 0.49, p = 0.003). The mean expression values of E-cad in both good differentiated group(257.5±165.4) and moderate differentiated group(138.3±72.0) are significant higher than that in poor differentiated group(74.2±38.6), respectively(p =0.01 and p =0.02). Significant difference of expression of E-cad also was found between metastasis(97.5±68.0) and non-metastasis group(227.3±30.1), p = 0.002.The mean expression values of PCNA in squamous cell carcinomas (182.2±67.8) and that in adenocarcinomas(165.4±65.8) has no significant difference(p =0.49). However, the expression value of PCNA has negative correlation with histological differentiation degree(r=-0.51, p = 0.018). The mean expression values of PCNA in both good differentiated group(147.3±61.5) and moderate differentiated group(160.2±55.5) are significantly lower than that in poor differentiated group(230.6±63.6), respectively(p =0.015 and p =0.009). Significant difference of expression of PCNA also was found between metastasis(204.7±58.3) and non-metastasis group(133.4±52.6), p =0.001.The E-cad and the PCNA expression present a negative correlation ( r=-0.51, p=0.002).Conclusions: E-cad expression is not significantly related to the histological type of NSCLCs. but significantly correlated with histological differentiation and metastasis. Down regulation of E-cad expression affects proliferation of cancer cells. Combining examination of E-cadherin and PCNA expressions is a good method to estimate the NSCLCs biological behavior.