Immunohistochemical expression of connexin 43 and NEDD9 in gastric cancer

Abstract

Najvažnije karakteristike karcinoma želuca su invazivnost i veliki metastatski potencijal. Sve je više dokaza da koneksini koji izgrađuju međustanična pukotinasta spojišta i NEDD9 protein igraju važnu ulogu u epitelno-mezenhimalnoj tranziciji i metastaziranju tumora različitih sijela. Cilj ovog istraživanja bio je odrediti i usporediti imunohistokemijsku izraženost koneksina 43 (Cx43) i NEDD9 u 108 uzoraka primarnog adenokarcinoma želuca (53 bez metastaza i 55 s metastazama u limfne čvorove) te korelirati njihovu izraženost s različitim kliničkim i patohistološkim parametrima. U našem istraživanju većina karcinoma nije izražavala Cx43 u epitelnoj komponenti, dok je u stromi pokazala veću izraženost (P<0,001). Izraženost Cx43 u stromi korelirala je s višim stadijem bolesti (P=0,03) i veličinom tumora (P=0,002). Većina karcinoma izražavala je NEDD9 istovremeno u epitelnoj i stromalnoj komponenti karcinoma. Izraženost NEDD9 bila je u značajnoj korelaciji s veličinom tumora (P=0,001), perineuralnom invazijom (P=0,049) te kliničkim stadijem bolesti (P<0,001). Neovisni loši prognostički čimbenici bili su jaka izraženost Cx43 u epitelu (HR 1.55, 95%CI 1.00 - 2.38, P=0.048), jaka izraženost NEDD9 u epitelu (HR 6.85, 95% CI 2.36 - 19.88, P<0.001) te viši T status (HR 1.54, 95% CI 1.07 - 2.20, P=0.019) i viši N status (HR 1.63, 95% CI 1.29 - 2.08, P<0.001). Potrebna su daljnja istraživanja na većem uzorku karcinoma želuca i njihovim metastatskim sijelima kako bi se potvrdio prognostički značaj Cx43 i NEDD9.Invasive growth and metastatic potential are considered to be the most important features of gastric cancer. Growing evidence suggests that connexins, who form intercellular gap junctions, and NEDD9 protein have an important role in epithelial-mesenchymal transition and metastasis of cancer of various primary sites. Aim of this study was to determine and correlate immunohystochemical expression of connexin 43 (Cx43) and NEDD9 in 108 samples of gastric adenocarcinoma (53 without and 55 with lymph node involvement) with various clinical and pathohystological parameters. According to our results, most cancers didn't express Cx43 in cancer cells but demonstrated expression in the stroma (P <0.001). Stromal Cx43 expression correlated both with higher disease stage (P=0.03) and size of the tumor (P=0.002). Most cancers expressed NEDD9 simultaneously in epithelial and stromal component. NEDD9 expression correlated with tumor size (P=.001), perineural invasion (P=.049) and clinical disease stage (P<.001). Increased epithelial Cx43 expression (HR 1.55, 95%CI 1.00 - 2.38, P=0.048), increased epithelial NEDD9 expression (HR 6.85, 95% CI 2.36 - 19.88, P<0.001), advanced T status (HR 1.54, 95% CI 1.07 - 2.20, P=0.019) and advanced N status (HR 1.63, 95% CI 1.29 - 2.08, P<0.001) were identified to be independent predictors of poor prognosis. These findings warrant further investigation in larger cohorts of patients with gastric cancer and various metastatic sites