RESUMO
Aims: Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) are members of the glycosylphosphatidylinositol (GPI)-linked immunoglobulin (Ig) superfamily and take part in regulation of cell adhesion, tumor suppression and angiogenesis. Overexpression of CEACAM 1, 5 and 6 is widely described in several gastrointestinal epithelial tumors. The aim of study was to evaluate the expression of CEACAM 1, CEACAM 5 and CEACAM 6 in the most common precursor lesions of pancreatic ductal adenocarcinoma -pancreatic intraepithelial neoplasia (PanIN). Methods and results: The study group consisted of 32 patients treated for chronic pancreatitis and 38 patients with pancreatic ductal adenocarcinoma who also had pancreatic intraepithelial neoplasia. The expression of CEACAM was performed by immunohistochemical method and evaluated using 3-point scale: 0 - lack of positive reaction in pancreatic intraepithelial neoplasia, 1 (weak and moderate) - reaction present in 1-30% epithelial cells in PanIN and 2 (strong) - reaction present in >30% epithelial cells in PanIN. Expression of CEACAM 1, 5 and 6 increased with increasing degree of advancement of PanIN. Differences in expression of CEACAM 1, 5 and 6 between normal pancreatic ducts and different degrees of PanIN were statistically significant (p<0.001). We observed relationship between CEACAM1 expression and localization of PanIN in different parts of the pancreas. Conclusions: CEACAM 1, CEACAM 5 and CEACAM 6 expression appears to be an early event in pancreatic carcinogenesis. Moreover, expression of CEACAM 1, 5 and 6 may represent a useful biomarker that may aid in the identification of precancerous lesions in the pancreas.
Assuntos
Adenocarcinoma/genética , Antígenos CD/genética , Antígeno Carcinoembrionário/genética , Carcinoma Ductal Pancreático/genética , Moléculas de Adesão Celular/genética , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/genética , Carcinogênese/genética , Carcinoma in Situ/complicações , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Carcinoma Ductal Pancreático/patologia , Feminino , Proteínas Ligadas por GPI/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/metabolismo , Pâncreas/patologia , Pancreatite Crônica/complicações , Pancreatite Crônica/genética , Pancreatite Crônica/patologiaRESUMO
Tensins belong to the family of adhesion proteins which form focal adhesions serving as a bridge between the extracellular matrix and intracellular actin skeleton. The tensin family consists of four members (tensin-1 to -4) which are widely expressed in normal and cancerous tissues. The presence of Src homology 2 and phosphotyrosine binding domains is a unique feature of tensins which enables them to interact with tyrosine-phosphorylated proteins in PI3K/Akt and ß-integrin/FAK signaling pathways. The tensin-mediated signaling pathway regulates physiological processes including cell motility and cytoskeleton integrity. The expression of tensins varies among cancers. Several papers report tensins as tumor suppressive proteins, whereas tensins may promote epithelial to mesenchymal transition and cancer cell metastasis. Recent findings and further research on tensins as therapeutic targets in cancers may contribute to identifying effective anti-cancer therapy. In this review we focus on the role of tensins in normal and cancer cells. We discuss potential mechanism(s) involved in carcinogenesis.
RESUMO
Tensins belong to the group of adhesion proteins that are involved in cell adhesion and migration, actin cytoskeleton maintenance and intercellular communication. TNS1, TNS2 and TNS3 proteins expression was evaluated in 90 patients with gastric cancer by immunohistochemistry method. TNS1 was more frequently present in non-differentiated tumors compared to poorly and moderately differentiated tumors (p = 0.016). TNS1 was also more often observed in metastatic tumors compared to those without distant metastases (p = 0.001). TNS2 was more common in moderately differentiated tumors than in poorly or non-differentiated ones (p = 0.041). TNS2 expression was also more frequently present in tumors with peritumoral inflammation (p = 0.041) and with concomitant H. pylori infection (p = 0.023). In contrast, TNS3 protein was more prevalent in moderately than in poorly and non-differentiated tumors (p = 0.023). No significant relationship was found between tensins' expression and the overall survival rate of patients. TNS1 protein expression is associated with a poor-prognosis type of GC. Higher expression of TNS2 is accompanied by peritumoral inflammation and H. pylori infection, which favor the development of GC of a better prognosis, similarly to higher TNS3 protein expression.
Assuntos
Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Tensinas/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Adesão Celular/fisiologia , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Tensinas/genética , Tensinas/fisiologiaRESUMO
BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors worldwide. Tensin 4 (TNS4) is an adhesive protein belonging to the tensin family. This protein is located in focal adhesion sites. The TNS4 gene is considered an oncogene in numerous cancers. This protein plays an important role in adhesion, migration and proliferation of cells. AIM: To evaluate expression of TNS4 protein in GC tissues and analysis of the clinical and histopathological parameters as well as the overall survival rate of patients. METHODS: The expression of TNS4 was assessed in 89 patients using immunohistochemistry. RESULTS: Positive expression of TNS4 was observed in 49 of 89 patients (55.06%). Higher TNS4 expression was more common in GC tumors with a diameter ≥ 5 cm (P = 0.040). We demonstrated that an increase in TNS4 expression was more frequent in tumors of the histological type without mucinous components than in tumors from mucosal cancers (P = 0.023). Furthermore, TNS4 expression was higher in moderately differentiated tumors than in poorly differentiated and non-differentiated tumors (P = 0.002). Increased TNS4 expression was also noted in the intestinal type of GC according to Lauren's classification (P = 0.020). No statistically significant correlation was found between the expression of TNS4 and the overall survival rate of patients. CONCLUSION: TNS4 expression was significantly higher in tumors with a diameter ≥ 5 cm of the moderately differentiated intestinal type (according to Lauren's classification) of GC without a mucinous component. Therefore, increased TNS4 expression is related to the histological type of GC with a better prognosis.