Expression and Concentration of Matrix Metalloproteinase 9 and Tissue Inhibitor of Matrix Metalloproteinases 1 in Laryngeal Squamous Cell Carcinoma.

The aim of this study was to assess the expression of MMP-9 and TIMP-1 in cancerous tissue as well as in the serum and plasma concentrations of these proteins in patients with laryngeal cancer and compare the results to the inflammatory reaction in healthy subjects. Twenty-seven patients who were diagnosed with laryngeal carcinoma and selected for total laryngectomy were included in the study group. MMP-9 and TIMP-1 expression in tissues was assessed using immunohistochemical assays. Immunoenzymatic ELISA methods were used to measure MMP-9 and TIMP-1 concentrations in serum and plasma. MMP-9 and TIMP-1 were identified in tumor cells and in the tumor stroma compartment, as well as in macroscopically healthy mucous membrane. MMP-9 expression was more significant in tumor stroma than in the perimatrix of the mucous membrane (p = 0.047). TIMP-1 expression was significantly higher in the matrix and perimatrix of the mucous membrane than in cancer tissue (p = 0.0093) and the tumor stroma compartment (p < 0.0001). Expression of TIMP-1 was observed more frequently in tumors without infiltrated lymph nodes (p = 0.009). Serum concentrations of MMP-9 and TIMP-1 as well as plasma TIMP-1 concentration were significantly higher in the study group than in the control group (p = 0.0004, p = 0.002, and p = 0.0001, respectively). A significantly higher TIMP-1 level in plasma was found in patients with poorly differentiated tumors compared to G1 and G2 (p = 0.046). MMP-9/TIMP-1 rate in serum was significantly higher in the study group than in the control group. The balance between the level of MMP-9 and TIMP-1 is disrupted in laryngeal cancer. The significant correlation between TIMP-1 expression and the presence of lymph node metastases, as well as that between TIMP-1 plasma concentration and stage of cancer histological differentiation, might indicate the importance of this molecule as a prognostic factor during carcinogenesis.

The added value of magnifying endoscopy in diagnosing patients with certain gastroesophageal reflux disease.

PURPOSE: In most cases gastroesophageal reflux disease proceeds without macroscopic erosions in the esophagus. We aimed to clarify if abnormalities detectable in magnifying endoscopy may offer additional diagnostic criteria for gastroesophageal reflux disease and to what histopathologic structures do they correspond. PATIENTS/METHODS: Esophageal mucosa above and below Z-line was evaluated under x115 magnification in 67 gastroesophageal reflux disease patients (11 with erosive reflux disease, 28 with Barrett's esophagus, 28 with nonerosive reflux disease) and in 12 patients without gastroesophageal reflux disease (negative control group). Features characteristic of gastroesophageal reflux disease were specified by comparing erosive reflux disease and Barrett's esophagus patients with negative control group. Afterwards the presence of identified features were evaluated in nonerosive reflux disease group. Interobserver agreement in the recognition of the proposed criteria was rated. Biopsies collected from the mucosa above Z-line were evaluated histologically after hematoxylin and eosin staining. RESULTS: Endoscopic lesions characteristic of gastroesophageal reflux disease were: microerosions, abnormal intrapapillary capillary loops, obscured palisade vessels, white points, big triangular indentations of Z-line and villous mucosa below Z-line. The presence of two or more of the above features indicated gastroesophageal reflux disease with 97% sensitivity and 75% specificity. Substantial interobserver agreement was achieved in evaluation of obscured palisade vessels, abnormal intrapapillary capillary loops and white points. Endoscopic lesions were correlated to histology. Lesions identified with magnifying endoscopy were helpful in discerning between negative control group and nonerosive reflux disease patients. CONCLUSIONS: Magnifying endoscopy reveals abnormalities that can be used as additional endoscopic diagnostic criteria of gastroesophageal reflux disease.

Expression of chosen cell cycle and proliferation markers in pancreatic intraepithelial neoplasia.

INTRODUCTION: Pancreatic ductal adenocarcinoma is one of the most aggressive tumours that develops from precursor lesions, most frequently including pancreatic intraepithelial neoplasia (PanIN). Deregulation of the cell cycle, responsible for uncontrolled cell proliferation, is an important phenomenon in the development of this cancer. AIM: To evaluate the cell cycle and the expression of proliferation markers, namely Ki67, PCNA, and cyclin D1 in pancreatic intraepithelial neoplasia at its different stages of progression. MATERIAL AND METHODS: The study group consisted of 70 patients with different pancreatic diseases (pancreatic ductal adenocarcinoma, pancreatitis, and pancreatic cysts), who also had pancreatic intraepithelial neoplasia. Expression of Ki67, PCNA, and Cyclin D1 was analysed immunohistochemically using appropriate antibodies. RESULTS: Statistically significant differences were demonstrated in Ki67, PCNA, and Cyclin D1 expression between normal pancreatic ducts and various stages of PanIN (p < 0.001). Expression of these proteins increased from normal pancreas to PanIN 1, 2, and 3. Expression of these proteins was higher in stages PanIN 1, 2, and 3 compared to normal pancreas. The expression of Ki67, PCNA, and cyclin D1 was associated with age (p < 0.001), Ki67 and PCNA with sex (p < 0.001), and PCNA with the type of primary disease (p = 0.031). Simultaneously, a directly proportional relationship was established between the expression of all proteins examined (p < 0.001). CONCLUSIONS: An increase in the expression of Ki67, PCNA, and cyclin D1 suggests that these proteins may enhance epithelial cell proliferation and may influence the development of pancreatic intraepithelial neoplasia. Moreover, immunohistochemical assessment of Ki67, PCNA, and cyclin D1 expression may be helpful in the differential diagnosis of PanIN.

p16, p21, and p53 proteins play an important role in development of pancreatic intraepithelial neoplastic.

BACKGROUND: Deregulation of cell cycle takes place during the development of many cancers as well as pancreatic ductal adenocarcinoma (PDA), which develops from precursor lesions, most frequently including pancreatic intraepithelial neoplasia (PanIN). AIMS: The aim of this study was to evaluate and compare the expression of p16, p21, and p53 proteins taking part in the regulation of the cell cycle in normal pancreatic ducts and pancreatic intraepithelial neoplasia at its various advancing stages. METHODS: The expressions of p16, p21, and p53 were assessed immunohistochemically in 70 patients with different pancreatic diseases (pancreatic ductal adenocarcinoma, pancreatitis, and pancreatic cysts), showing also pancreatic intraepithelial neoplasia. The results correlated with chosen clinicopathological parameters. RESULTS: Our study revealed a difference in p16, p21, and p53 expressions between normal pancreatic ducts and various stages of PanIN. p16 expression progressively decreased, whereas p21 and p53 increased from normal pancreas to PanIN 1, 2, and 3. The expression of p21 was associated with age, p53 with PanIN location in the pancreas and p16 with the type of primary diseases. Simultaneously, we observed a directly proportional relationship between the expression of p21 and p53 proteins and inversely proportional between the p16 and the p21 and p53 proteins. CONCLUSIONS: p16, p21, and p53 proteins play an important role in the deregulation of the cell cycle and participate in the development of pancreatic intraepithelial neoplasia. Immunohistochemical evaluation of their expressions may be helpful in the diagnosis of PanIN.

The Association between Elevated Levels of Peripheral Serotonin and Its Metabolite - 5-Hydroxyindoleacetic Acid and Bone Strength and Metabolism in Growing Rats with Mild Experimental Chronic Kidney Disease.

Chronic kidney disease (CKD) is associated with disturbances in bone strength and metabolism. The alterations of the serotonergic system are also observed in CKD. We used the 5/6 nephrectomy model of CKD to assess the impact of peripheral serotonin and its metabolite- 5-hydroxyindoleacetic acid on bone biomechanical properties and metabolism in growing rats. The animals were sacrificed one and three months after nephrectomy. Biomechanical properties were determined on two different bone types: the cortical bone of the femoral diaphysis using three-point bending test and the mixed cortico-trabecular bone by the bending test of the femoral neck. Biomechanical tests revealed preserved cortical bone strength, whereas work to fracture (W) and yield load (Fy) of mixed cortico-trabecular bone were significantly lower in CKD compared to controls. Serum activity of alkaline phosphatase (ALP), a bone formation marker, and tartrate-resistant acid phosphatase (TRACP 5b) reflecting bone resorption, were similar in CKD and controls. ALP was associated with lower femoral stiffness and strength, and higher displacements and W. TRACP 5b was inversely associated with cortical Fu and W. The elevated peripheral serotonergic system in CKD was: inversely associated with stiffness but positively related to the displacements and W; inversely associated with cortical Fy but positively correlated with this parameter in cortico-trabecular bone; inversely associated with ALP in controls but positively correlated with this biomarker in CKD animals. In conclusion, this study demonstrates the distinct effect of mild degree of CKD on bone strength in rapidly growing rats. The impaired renal function affects the peripheral serotonin metabolism, which in turn may influence the strength and metabolism of bones in these rats. This relationship seems to be beneficial on the biomechanical properties of the cortico-trabecular bone, whereas the cortical bone strength can be potentially reduced.

Expressions of Matrix Metalloproteinases 2, 7, and 9 in Carcinogenesis of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease, usually diagnosed in an advanced stage which gives a slight chance of recovery. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that participate in tissue remodeling and stimulate neovascularization and inflammatory response. The aim of the study was to evaluate the expression of MMP-2, MMP-7, and MMP-9 in normal ducts, tumor pancreatic adenocarcinoma cells, and peritumoral stroma in correlation with clinicohistopathological parameters. The study material was obtained from 29 patients with pancreatic ductal adenocarcinoma. The expressions of MMP-2, MMP-7, and MMP-9 were performed by immunohistochemical technique. Microvessel density (MVD) was visualized by special immunostaining. The expressions of MMP-2, MMP-7, and MMP-9 were mainly observed in tumor cells and peritumoral stroma. MMP-2 expression in cancer cells was correlated with female gender, stronger inflammation, and histopathological type of cancer (R = 0.460, p = 0.013; R = 0.690, p = 0.0001; R = -0.440, p = 0.005, resp.). The expression of MMP-7 in tumor cells was found to positively correlate with the presence of necrosis and negatively correlate with MVD (R = 0.402, p = 0.031; R = -0.682, p = 0.000). We also showed that positive MMP-9 expression in tumor cells was associated with MVD (R = 0.368, p = 0.084); however, it was not statistically significant. Our results demonstrate that MMP-2, MMP-7, and MMP-9 expressions correlate with various morphological features of the PDAC tumor such as inflammation, necrosis, and formation of the new blood vessels.

Expression of CD117, DOG-1, and IGF-1R in gastrointestinal stromal tumours - an analysis of 70 cases from 2004 to 2010.

INTRODUCTION: Determination of the type of mutations in gastrointestinal stromal tumours (GIST) plays a major role in assessing the risk of progression of the disease, and also allows determination of the clinical management and treatment. More accurate GIST diagnosis is possible by using simultaneously various types of antibodies to immunohistochemistry methods in routine procedures. AIM: To evaluate the expression of CD117, DOG-1, and IGF-1R in patients with gastrointestinal stromal tumours, and analysis of the impact of the examined protein expression on patient survival with emphasis on specific recognition and prognostication of these tumours. MATERIAL AND METHODS: The protein expression was analyzed in 70 patients who had undergone surgical treatment for mesenchymal tumours of the gastrointestinal tract, using the immunohistochemical method. RESULTS: Positive expression of CD117, DOG-1, and IGF1R included 95.71%, 88.57% and 11.43% of study GISTs, respectively. Statistical analysis showed positive significant correlation between DOG-1 expression and histological type of tumour (p = 0.024). Analysis of overall survival curves of 70 GIST patients according to expression of CD117, DOG-1, and IGF1R did not show a tendency towards longer survival of patients with positive expression (p > 0.05). CONCLUSIONS: Predictive factors determining the survival time of patients are strongly associated with morphological features of tumours. A thorough analysis of each case plays a key role in predicting survival time of patients and may be a clue in targeting the therapeutic procedure.

Expressions of Matrix Metalloproteinases (MMP-2, MMP-7, and MMP-9) and Their Inhibitors (TIMP-1, TIMP-2) in Inflammatory Bowel Diseases.

Crohn's disease (CD) and ulcerative colitis (UC) belong to a group of inflammatory bowel diseases (IBD). The aim of our study was to evaluate the expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 in ulcerative colitis and Crohn's disease. The study group comprised 34 patients with UC and 10 patients with CD. Evaluation of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 expression in tissue samples was performed using immunohistochemistry. The overexpression of MMP-9 and TIMP-1 was dominant in both the glandular epithelium and inflammatory infiltration in UC patients. In contrast, in CD subjects the positive expression of MMP-2 and TIMP-1 was in glandular tubes while mainly MMP-7 and TIMP-2 expression was in inflammatory infiltration. Metalloproteinases' expression was associated with the presence of erosions, architectural tissue changes, and inflammatory infiltration in the lamina propria of UC patients. The expression of metalloproteinase inhibitors correlated with the presence of eosinophils and neutrophils in UC and granulomas in CD patients. Our studies indicate that the overexpression of metalloproteinases and weaker expression of their inhibitors may determine the development of IBD. It appears that MMP-2, MMP-7, and MMP-9 may be a potential therapeutic target and the use of their inhibitors may significantly reduce UC progression.

Dysfunctions in the Mature Dendritic Cells Are Associated with the Presence of Metastases of Colorectal Cancer in the Surrounding Lymph Nodes.

Dendritic cells play a key role in the antigen presentation and T cell activation. The aim of this study was a detailed analysis of the presence of mature dendritic cells (CD 83 positive) in colorectal cancer in correlation with selected clinicopathological parameters. The presence of mature dendritic cells (mDCs) was determined immunohistochemically using the anti-CD83 antibody. The morphometric analysis of the mDCs was performed in the normal colon wall adjacent to the cancerous tumor as well as in the front of the tumor and in the main mass of the cancerous tumor. Decrease in mDCs in the front and in the main tumor mass was observed. The increase in the number of mDCs in both of these locations was associated with the presence of metastases in the nearby lymph nodes (p < 0.05 and p < 0.01). Furthermore, the increase in the proportion of mDCs in the main tumor mass was associated with the presence of the invasion of tumor cells into the blood and lymph vessels (p < 0.01). The increase in the amount of mDCs in the cancerous tumor is associated with the invasiveness of the tumor and especially with the metastasis to the surrounding lymph nodes.

Diagnostic value of matrix metalloproteinase 9 and tissue inhibitor of matrix metalloproteinases 1 in cholesteatoma.

OBJECTIVES: Matrix metalloproteinase 9 (MMP-9), able to degrade type IV collagen, plays a key role in inflammatory cell migration as well as in the destructive behaviour of cholesteatoma. The aim of our study was to compare the expression of MMP-9 and TIMP-1 in cholesteatoma tissue and in the concentrations in serum and plasma concentrations. MATERIAL AND METHODS: Twenty five adult patients suffering from cholesteatoma (a study group) were included in the study. A comparison group consisted of 25 adult patients admitted to hospital due to nasal septum deviation. MM-9 and TIMP-1 serum and plasma concentrations as well as proteins' expressions in cholesteatoma tissues (study group) and normal retroauricular skin specimens (control group) were evaluated. MMP-9 and TIMP-1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Cholesteatoma tissues and normal retroauricular skin specimens were evaluated immunohistochemically. RESULTS: In the study and a comparison groups, MMP-9 and TIMP-1 concentrations were similar with no significant difference within the groups. In cholesteatoma tissues, the expression of the investigated enzyme and its inhibitor was higher than in normal skin specimens, limited mostly to cholesteatoma perimatrix. CONCLUSION: Cholesteatoma may be limited to the middle ear or parts of the temporal bones. Our findings suggest better clinical usefulness of MMP-9 and TIMP-1 expression in cholesteatoma tissues than either serum or plasma levels of these proteins. It might suggest that the higher the expression of MMP-9 the stronger the inflammation -accompanied cholesteatoma.

Mesenteric lymphadenitis caused by Yersinia enterocolitica.

Yersiniosis is an acute or chronic, zoonotic disease caused by infection of Gram-negative rods Yersinia enterocolitica. It can be transmitted by the consumption of originally contaminated food products (pork, unpasteurized milk) or secondarily contaminated with animal or vegetable products. The clinical picture of infection may have a variable course is related to the age and physical condition of the patient, or pathogenic properties of microorganisms. Infection caused by Y. enterocolitica can occur in different clinical forms: food poisoning, colitis, mesentric lymphadenitis, erythema nodosum, arthritis, pharyngitis, pneumonia, meningitis, sepsis. The aim of this study was to present a rare case of infection with Y. enterocolitica mesenteric lymph nodes coexistent with appendicitis.

Ectopic Pancreas Imitating Gastrointestinal Stromal Tumor (GIST) In The Stomach.

Ectopic pancreas is a rare congenital disorder defined as pancreatic tissue lacking vascular or anatomic communication with the normal body of the pancreas. Most cases of ectopic pancreas are asymptomatic, but it may become clinically evident depending on the size, location and the pathological changes similar to those observed in case of the normal pancreas. It is often an incidental finding and can be located at different sites in the gastrointestinal tract. The most common locations are: the stomach, duodenum or the proximal part of small intestine. The risk of malignancy, bleeding and occlusion are the most serious complications. Despite the development in diagnostics, it still remains a challenge for the clinician to differentiate it from neoplasm. In this report, we described a case of 28-years old woman who presented recurrent epigastric pain. The upper gastrointestinal endoscopy revealed gastrointestinal stromal tumor on the border of the body and antrum of the back wall of great curvature of the stomach. The histopathological examination after surgery showed heterotopic pancreatic tissue. Ectopic pancreas should be considered in the differential diagnosis of gastric mass lesions.

The impact of Helicobacter pylori on EGF, EGF receptor, and the c-erb-B2 expression.

PURPOSE: Increased expression of epidermal growth factor (EGF), its receptor (EGFR), and c-erb-B2 protein, which is homological with the EGF receptor, in gastric mucosa, may play a role in gastric carcinogenesis. We assessed if the infection and eradication of Helicobacter pylori (H. pylori) affects the gastric expression of growth factors and serum gastrin concentrations. PATIENTS/METHODS: We examined immunohistochemically gastric EGF and both receptors' expression in: gastric cancer (GC; n=29), chronic gastritis with H. pylori infection (GHp+; n=40) before and after eradication and in patients without H. pylori infection (GHp-; n=42). RESULTS: Before the eradication therapy, gastric mucosal EGF and both receptor's expressions in GHp+ patients were increased compared to GHp- (p<0.05), but were similar to GC. After eradication, EGF and the receptor's expression significantly decreased in the gastric body. Both EGFR and c-erb-B2 expression in the antrum were still higher than in GHp- (p<0.05), and remained comparable to GC. CONCLUSIONS: In patients with H. pylori infection the gastric mucosal EGF, EGFR, and c-erb-B2 expressions are similar to those observed in gastric cancer. The persistence of the antral expression of receptors after eradication, at a level comparable to the gastric cancer group, suggests their eventual role in the progression of changes initiated by H. pylori toward carcinogenesis.

Epidermal cyst of the spleen--a rare case in clinical practice.

Splenic cysts are rare disease that are diagnosed incidentally during imaging studies. In recent years, through the development of diagnostic methods the detection of their are increased, although documented and described in the literature of cases is still low. The disease can be asymptomatic--this concerns mainly small cysts, but greater changes cause unspecific symptoms resulting from oppression of enlarged spleen on adjacent organs. Due to the etiology of cysts, they are divided into primordial and false. Primordial cysts have an epithelial lining which distinguishes them from false and they are divided into parasitic and nonparasitic. Because of the possibility of complications cysts usually treated surgically, with the aim to preserve the splenic parenchyma. We present a case of a 28-year-old woman who has revealed the presence of epidermal cysts of the spleen.

Ménétrier's disease, a premalignant condition, with coexisting advanced gastric cancer: A case report and review of the literature.

Ménétrier's disease (MD) is a rare type of hypertrophic gastropathy involving the body of the stomach, which is characterized by thickening of the mucous membrane in the form of giant rugal folds, hypochlorhydria and protein loss. The potential for malignant transformation of this lesion remains a controversial topic. Therefore, in the present study, a case of a 51-year-old male exhibiting MD with coexisting advanced gastric cancer is described; a review of the literature is also presented. The present case emphasized that MD requires particular attention and should be regarded as a premalignant condition due to the previously documented cases of its coexistence with gastric cancer, in addition to the lack of knowledge regarding its pathogenesis and effective therapeutic management.

High Fas expression in gastric carcinoma cells as a factor correlating with the occurrence of metastases to regional lymph nodes.

PURPOSE: The aim of this study was to evaluate the correlation of the expression of Fas and Fas-L proteins in gastric carcinoma cells on the occurrence of metastases to regional lymph nodes. MATERIAL/METHODS: The study included 89 patients treated surgically for gastric carcinoma. The evaluated clinicomorphological parameters were verified based on both histopathological material collected at surgery and intraoperative image. Fas and Fas-L expression was evaluated immunohistochemically in the neoplastic tissue of the removed gastric tumors. RESULTS: A statistically significant positive correlation between Fas expression in gastric carcinoma cells and the number of regional lymph nodes affected by metastases was observed (p<0.05). No such correlation was noticed with respect to Fas-L. A statistically significant correlation between the depth of neoplastic infiltration of the stomach wall (T feature) and the number of affected lymph nodes was observed (p<0.05). No statistically significant correlations in the other examined clinicomorphological features and the number of metastatic lymph nodes was observed. CONCLUSION: A positive Fas expression correlates with more frequent occurrence of metastases to regional lymph nodes. Determination of this protein expression in cancer cells prior to surgery may be helpful for planning the surgical procedure, especially with respect to the extent of lymph node excision.

The expression of Bcl-2 and BID in gastric cancer cells.

BACKGROUND: Bcl-2 and BID play a major role in the process of apoptosis and their dysfunction underlies carcinogenesis. The study objective was to assess the expression of Bcl-2 and BID in gastric cancer cells in correlation with chosen clinicopathological parameters, presence of Helicobacter pylori infection, and patients' survival. MATERIALS AND METHODS: The study involved 88 patients operated on for gastric cancer. The expressions of Bcl-2 and BID were determined immunohistochemically. RESULTS: Positive Bcl-2 expression was found in 55.7% and, BID in 53.6% of patients. The Bcl-2 expression correlated with stage pT3 and T4 gastric cancer (P < 0.05), with the intestinal type according to Lauren (P < 0.001), ulcerated type according to Bormann's classification (P < 0.01), and with local lymph node metastases (P < 0.05). CONCLUSION: The Bcl-2 protein plays a key role in the process of gastric cancer formation and is associated with the growth of definite types of gastric cancer.

PRL-3 and E-cadherin show mutual interactions and participate in lymph node metastasis formation in gastric cancer.

E-cadherin, a transmembrane adhesion molecule, and phosphatase of regenerating liver 3 (PRL-3) protein, a member of the family of tyrosine phosphatases, seem to be responsible for cancer cell migration. Therefore, the study objective was to determine a correlation between PRL-3 and E-cadherin, to assess their expression in neoplastic tissue and normal mucosa of the stomach, to analyze their effect on cancer advancement, and to evaluate their potential as prognostic markers in gastric cancer. The expressions of PRL-3 and E-cadherin were assessed immunohistochemically in 71 patients with gastric cancer. Positive expression of PRL-3 was observed in 42.2 % of gastric cancer cases, whereas E-cadherin expression was abnormal in 38 % of cases. The study revealed that the positive PRL-3 expression and abnormal E-cadherin expression were associated with mucinous gastric carcinoma and lymph node involvement. The former was also related to the infiltrating type of tumor and abnormal E-cadherin expression. The expression of PRL-3, but not of E-cadherin, was associated with shorter survival of patients. PRL-3 and E-cadherin exhibit interactions in gastric cancer and are involved in the formation of lymph node metastases. The PRL-3 protein can be an independent predictive factor of overall survival in gastric cancer patients.

Bax protein may influence the invasion of colorectal cancer.

AIM: To evaluate the expression of Bcl-xL, Bak, and Bax proteins in correlation with particular clinico-histopathological parameters, including tumor invasion front, in patients with colorectal cancer. METHODS: The expression of these proteins was evaluated with the use of the immunohistochemical method in 50 primary tumors. RESULTS: According to observations, a low expression of Bax and Bak proteins is related to the localization of the tumor in the rectum (P < 0.05 and P < 0.05 respectively), which may explain an increased incidence of colorectal cancer in this area. A positive expression of Bax protein also correlates with the presence of cancer cell infiltration to lymph and blood vessels (P < 0.05), which may suggest the participation of this protein in the early stages of colorectal cancer progression. Moreover, a positive expression of Bcl-xL protein correlated with a positive expression of Bak protein. This may suggest a greater participation of Bcl-xL protein in the inhibition of the proapoptotic Bak protein, but not the Bax protein. CONCLUSION: Bax protein is probably very significant in the cancerogenesis mechanism in the large intestine.

Serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinases 2 (TIMP-2) in colorectal cancer patients.

The objective of the study was the assessment of serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in patients with colorectal cancer (CRC). The study included 72 CRC patients and 68 healthy subjects. The serum levels of MMP-2 and TIMP-2 were measured using enzyme-linked immunosorbent assay (ELISA) method, whereas tissue expression of MMP-2 and TIMP-2 in cancer cells, interstitial inflammatory cells, and adjacent normal colorectal mucosa were examined by immunohistochemical staining of tumor samples. The serum levels of MMP-2 and TIMP-2 in cancer patients were significantly lower than those in control group, but the percentage of positive immunoreactivity of these proteins were higher in malignant and inflammatory cells as compared to normal tissue. There was a significant correlation between MMP-2 immunoreactivity in inflammatory cells and the presence of distant metastases and between TIMP-2 expression in inflammatory cells and tumor size, nodal involvement, and distant metastases. Area under receiver operating characteristic (ROC) curve (AUC) for serum MMP-2 was higher than for serum TIMP-2. Moreover, positive tissue expression of MMP-2 was a significant prognostic factor for CRC patients' survival. Our findings suggest that MMP-2 and TIMP-2 might play a role in the process of colorectal cancer invasion and metastasis, but the significance of their interactions with tumor stroma and interstitial inflammatory infiltration in colorectal neoplasia require further elucidation.