Jolanta Czyzewska

The expression of E-cadherin-catenin complex in patients with advanced gastric cancer: role in formation of metastasis

The E-cadherin-catenin complex plays an important role in the process of cell adhesion. Its dysfunction is associated with a decrease in cell differentiation and with increased invasiveness and metastasis. Our aim was to evaluate the expression of E-cadherin and B-catenin in advanced gastric cancer in relation to selected clinico-pathomorphological parameters. Formalin-fixed, paraffin-embedded tissue specimens were immunohistochemically stained with monoclonal antibodies E-cadherin (NCL-E-Cad, Novocastra Laboratiries Ltd; dilution 1:50), beta-catenin (NCL-B-CAT, Novocastra Laboratories Ltd; dilution 1:100), alpha-catenin (alpha-E-caten, Santa Cruz Biotechnology; dilution 1:300) and gamma-catenin (gamma-catenin, Santa Cruz Biotechnology; dilution 1:100). The expressions of E-cadherin and alpha-, beta-, gamma-catenins in the main mass of tumor and lymph node metastasis were investigated in 91 patients with gastric cancer. No statistically significant correlation was observed between the expressions of E-cadherin, alpha-, beta-catenins and histological differentiation and between the expressions of E-cadherin, alpha-, gamma-catenins and location or depth of invasion. Moreover, the expression of alpha-, gamma-catenins in the main mass of tumor was not associated with lymph node metastasis. However, we found a relationship between the expression of beta-catenin in the main mass of tumor and lymph node metastasis and tumor location. The depth of invasion was correlated with positive expression of beta-catenin in the main mass of gastric cancer. A statistically significant association was observed between the expressions of E-cadherin and beta-catenin in the main mass of tumor and lymph node involvement. The expression of alpha-catenin in the main mass of tumor was also associated with histological differentiation and Laurens classification. Statistical analysis showed an association between the expression of E-cadherin and postoperative survival time. No significant correlation was found between the expression of alpha-, beta-, gamma-catenins and survival time. Our results may suggest that the E-cadherin-catenin complex is the factor indicative of metastasis and disease progression in gastric cancer. Also the expression of E-cadherin may play a role as a prognostic factor.

Correlation between Fas and FasL proteins expression in normal gastric mucosa and gastric cancer

The studys objective was to assess the expressions of Fas and FasL proteins in gastric cancer in correlation with chosen clinicohistological parameters. Fas and FasL expression was analyzed in 68 patients with gastric cancer, using the immunohistochemical method. The expression of Fas was found to be lower in gastric cancer cells than in healthy mucosa, both in the lining epithelium and in glandular tubes (28% vs. 48% and 44%; p < 0.001). The expression of FasL was also markedly lower in cancer cells than in glandular tubes, yet higher than in the lining epithelium (51% vs. 73% and 14%; p < 0.01). Positive expressions of FasL and Fas were lower in less advanced gastric cancer cells (T1, T2), than in more advanced tumors (T3, T4), but only in the case of FasL was this difference statistically significant (p < 0.05). Our findings seem to confirm the theory of the impact of apoptotic disorders at the level of Fas receptor and FasL protein in the process of gastric cancer formation and growth, which is manifested in the varied expressions of these proteins in gastric cancer and in the normal lining and glandular epithelium of the stomach. However, the lack of significant differences in the expressions of Fas and FasL in correlation to other clinicohistological parameters indicates the existence of mechanisms that have a greater impact on the process of differentiation of gastric cancers. This in our opinion eliminates these proteins as prognostic factors.

Expression of matrix metalloproteinase-9 in the neoplastic and interstitial inflammatory infiltrate cells in gastric cancer.

Matrix metalloproteinases (MMPs) play an important role in the extracellular matrix degradation, that is an essential step in tumor invasion and metastases. The current study objective was to evaluate the expression of MMP-9 in the neoplastic and in the interstitial inflammatory infiltrate cells in gastric cancer (GC). Moreover, the relationship between expression of this enzyme and clinicopathological features of GC, such as TNM stage, the depth of tumor invasion, lymph node and distant metastases were assessed. The study comprised 54 patients with gastric cancer. Immunohistochemistry was used to determine the expression of MMP-9 in gastric cancer cells. The semi-quantitative scale was applied to evaluate the expression of metalloproteinase-9. Immunohistochemical testing revealed a positive reaction of MMP-9 in 98% of all cancer tissue specimens and in 93% of inflammatory cells. The expression of MMP-9 in the neoplastic and inflammatory cells increased with more advance tumor stage, depth of tumor invasion and presence of lymph node as well as distant metastases. These findings indicate the significance of interstitial inflammatory infiltrate cells in the MMP-9 synthesis and the role of this enzyme in the invasiveness and metastatic potential of GC.

Correlation of c-erbB-2, EGF and EGFR expression with postoperative survival of patients with advanced carcinoma of the stomach.

The c-erbB-2 (HER-2/neu), EGF and EGFR (erbB-1) proteins, members of the epidermal growth factor receptor family, play a role in cell growth by binding to cell membrane receptors. The aim of the current study was to evaluate the expression of c-erbB-2, EGF and EGFR in advanced gastric carcinoma and to analyze its relationship with chosen anatomo-clinical parameters and prognosis. Standard avidin-biotin-peroxidase was used for c-erbB-2, EGF and EGFR immuno-histochemical staining (Novostain Super ABC Kit Universal); anti-human c-erbB-2 protein monoclonal antibody NCL-cerbB-2-316, anti-Epidermal Growth Factor monoclonal antibody (clone EGF-10) and EGFR goat polyclonal IgG (p-EGFR). A statistically significant correlation was found between c-erbB-2, EGF, EGRF expressions in the main mass of tumor and lymph node metastasis (p=0.000; p=0.000; p=0.00001, respectively). Also an association was observed between c-erbB-2 expression and Bormanns and Laurens classifications (p=0.05; p=0.006, respectively). Similarly, the expression of EGFR in main mass of tumor was correlated with the depth of invasion (p=0.007) and histological differentiation (p=0.04). Moreover, the expression of c-erbB-2 in the main mass of tumor and lymph node metastasis was associated with the age of the patients (p=0.03; p=0.0002 respectively). Strong association was found between the expression of EGRF in lymph node metastasis and histological differentiation (p=0.04). Positive expression of c-erbB-2 in lymph node metastasis was correlated with lymph node involvement (p=0.04). Positive expression of c-erbB-2 in the main mass of tumor and in lymph node metastasis was strongly correlated with postoperative survival (p=0.00001; p=0.003 respectively). We also found a relationship between EGF expression in gastric tumor and survival time (p=0.003). No association was noted between the expression of EGFR in the main mass of tumor and in lymph node metastasis and between the expression of EGF in lymph node metastasis and survival time. Our results suggest that the expression of c-erbB-2 and EGF protein can help predict the postoperative survival time.

Expression of the E-cadherin-catenin complex in patients with pancreatic ductal adenocarcinoma

Cadherins and catenins, mediators of intercellular interactions, play a major role in adhesion. Changes in their expression and functioning reflect invasive and metastatic properties of cancer cells. The study objective was to assess changes in the expressions of E-cadherin and alpha-, beta- and gamma-catenin proteins in pancreatic duct carcinoma in correlation with clinicopathological parameters, lymph node involvement and distant metastases. Twenty-nine patients with pancreatic duct carcinoma were analyzed in relation to gender and age, histological type, histological malignancy grade (G), local lymph node involvement and distant metastases. The expression levels of E-cadherin and alpha-, beta- and gamma-catenins were subjected to immunohistochemical labeling. Reduced expression or abnormal localization of E-cadherin and alpha-, beta- and gamma-catenins were observed in pancreatic duct carcinoma. The statistical analysis did not show any correlations of the expressions of these proteins with gender and age of patients, histological type (Hp), histological grade (G) and the presence of local lymph node involvement or distant metastases. However, correlations were found between the expression of E-cadherin and beta- catenin (p<0.001) as well of alpha-catenin with beta-catenin (p=0.006) and gamma-catenin (p=0.026). Disorders in the expression of E-cadherin reveal strong associations with abnormal expressions of alpha, beta- and gamma-catenins. Also enhanced tumor aggressiveness shows certain tendency correlations (although statistically insignificant) with the loss of E-cadherin expression and change in its localization.

Relationships between insulin-like growth factor i and selected clinico-morphological parameters in colorectal cancer patients.

UNLABELLED Insulin Like Growth Factor (IGF I) as the one of the strongest growth factors which can affect cancers development including colorectal cancer. IGF I induces processes of the cells growth and division. It regulates cells cycle and inhibits apoptosis. There is limited data about correlation between IGF I and staging of the tumor. The aim of the study was estimation of the clinical usefulness of IGF I concentration in the serum of the patients with colorectal cancer. MATERIAL AND METHODS We have examined 125 individuals with colorectal cancer. The age range was 36 to 92 years. They have been operated in the 2nd Departament of The Gastrointestinal Surgery of the Medical University in Białystok. Serum concentration of the IGF I have been estimated using immunoassay ELISA before and after operation. Correlation between serum level of IGF I and clinicopathologic features: age, gender, localisation of the primary tumor, TNM stage of tumor, histological type and histological grade (G) of the cancer have been estimated. RESULTS Our study revealed statistically significant increased serum concentration of IGF I in patients with locally advanced colorectal cancer (pT3 and pT4) comparing to less advanced (pT2) The investigations showed higher serum concentration of IGF I in patients with poorly differentiated cancers (G3) than in moderately differentiated. Similarly higher serum concentration of IGF I were found in male, in patients older than 60 years and in mucigenous colorectal cancers. CONCLUSIONS Our results indicated that IGF I can be one of the factors of the prognosis in colorectal cancer development.

Expression of epidermal growth factors and apoptosis markers in pancreatic ductal adenocarcinoma.

BACKGROUND Epidermal growth factor family members: EGF, EGFR and the c-erbB-2(HER-2/neu) are involved in the growth of pancreatic ductal carcinoma, its invasiveness and metastases. Similarly, proteins regulating apoptosis can influence the development of pancreatic cancer. The aim of our study was to assess the expressions of EGF, EGFR, c-erbB-2, Bax and Bcl-xL in comparison with anatomo-clinical parameters. We also analyzed the relationship between the epidermal growth factors and apoptosis-regulating proteins. MATERIALS AND METHODS The levels of these proteins were determined immunohistochemically in 29 pancreatic ductal carcinoma cases. RESULTS We found no correlation of EGF, EGFR, c-erbB-2, Bax and Bcl-xL with age and gender of patients, or histological type and grade of malignancy (G). However, we observed a very strong correlation between EGF, EGFR, Bax, Bcl-xL and lymph node metastases (p=0.000, p=0.001, p=0.008, p=0.012, respectively) and between EGF, EGFR and distant metastases (p=0.002, p=0.008, respectively). Moreover, we found a correlation between Bcl-xL and c-erbB-2 (p=0.030) and between EGF and Bax (p=0.041). CONCLUSIONS These investigations seem to suggest that both epidermal growth factors (EGF, EGFR) and apoptosis-regulating proteins (Bax and Bcl-xL) play an essential role in lymph node involvement. Moreover EGF and EGFR are involved in distant metastases. The apoptosis markers appear to cooperate with epidermal growth factor proteins in the process of tumor spread.

Helicobacter pylori infection and expressions of EGF, EGFR and c-erbB-2 proteins in gastric carcinoma.

The family of epidermal growth factor (EGF, EGFR, c-erbB-2) plays a pivotal role in gastric cancer progression, invasion and metastasizing. Helicobacter pylori infection is known to contribute significantly to the formation and progression of gastric cancer. However, the mechanisms responsible for this process have not been yet elucidated. We analysed the relationship between H. pylori infection and expression of proteins belonging to the family of epidermal growth factor (EGF, EGFR, c-erbB-2). Fifty-five patients with gastric cancer were analysed for Helicobacter pylori infection. The expressions of EGF, EGFR, c-erbB-2 proteins were determined using an immunohistochemical method. No statistically significant correlation was found between the degree of H. pylori infection and the expressions of EGF, EGFR and c-erbB-2 in gastric cancer. However, c-erbB-2 expression in the main mass of tumour correlated with tumour expression of EGF and EGFR and with c-erbB-2 expression in local lymph nodes. The expression of c-erbB-2 in lymph nodes was statistically significantly related to the expressions of EGF and EGFR both in the main mass of tumour and in lymph nodes. The expression of EGF was found to correlate with EGFR in the main mass of tumour and the expression of EGF in lymph nodes was related to lymph node EGFR level. Our study did not confirm the relationship between H. pylori infection and the expression of epidermal growth factor in gastric cancer.