Kolon tümörlerinde adenom-karsinom sekasında rol oynayan E-kaderini, β-katenin, C-MYC ve siklin D1 dağılımları

Abstract

SUMMARY THE E-CADHERIN, p-CATENIN, c-myc, AND CYCLIN-D1 THAT HAS BEEN SUGGESTED TO HAVE A ROLE IN ADENOMA-CARCINOMA SEQUENCE IN COLON TUMOURS It is reported that, colorectal cancers are the second common cause of cancer related death in western countries. The incidence of the cancer has been increasing. Colorectal polyps are also more common in developed countries particularly in western countries. The most of colorectal carcinomas are developed from adenomatous polyps and this process is known as adenoma-carcinoma sequence. This study was aimed to determine expression and cellular distribution of P-catenin and its relation with E-cadherin in adenoma-carcinoma sequence. We also studied cyclin-Dl and c-myc expression to investigate their possible interaction with cytopasmic and nuclear expression of p-catenin. In general, we aimed to investigate E-cadherin, P-catenin, cyclin-Dl, and c-myc expression patterns in colorectal polyps and tumours in respect to understand their possible roles in adenoma-carcinoma sequence. Following histopathological examination, 60 tumour samples and 3 1 polyp samples were taken from 61 patients diagnosed as colorectal carcinoma and polyp for the study. Immunohistochemical staining of E-cadherin, p-catenin, c-myc and cyclin-D I were performed each section of the cases. In this study, we show that, cytoplasmic and nuclear expression of P-catenin, nuclear expression of cyclin-Dl and decreased expression of E-caderin in polyps could be related with degree of dysplasia, suggesting that tliese proteins may have important roles in adenoma-carcinoma sequence. The nuclear expression of 3- catenin could be useful to detect invasive foci in polyps implicating that, nuclear expression of p-catenin may be used to detection of colorectal tumours in early 74ÖZET Kolorektal kanserler özellikle Batı ülkelerinde kanserle ilişkili ölümlerin ikinci önemli nedeni olarak karşımıza çıkmaktadır. Uzun bir süredir kolorektal kanser insidansında artış gözlenmektedir. Kolorektal poliplerde yine batı ülkeleri başta olmak üzere gelişmiş ülkelerde yaygın olarak görülmektedir. Kolorektal karsinomların çoğu adenomatöz poliplerden gelişmekte olup adenom-karsinom sekansı olarak isimlendirilmektedir. Bu çalışma, kolorektal karsinom ve eş zamanlı polip tanısı almış olgularda p-kateninin E-kaderinle ilişkisini, hücre içi ekspresyon dağılımını ve sitoplazmik ve/veya nükleer ekspresyonu durumunda Siklin Dİ ve c-myc genleri ile ilişkisini değerlendirmek, adenotna-karsinoma sekansında bu proteinlerin rolünü araştırmak, ayrıca tümörler ve poliplerdeki farklı E-kaderin, (3-katenin, Siklin Dİ ve c-myc ekspresyonlarmı saptayarak tanı ve prognostik önemini ortaya koymak amacıyla planlandı. Histopatolojik olarak değerlendirilerek kolorektal karsinom ve eş zamanlı polip tanısı almış 61 hastaya ait 60 tümör ve 31 polip olgusu çalışmaya alındı. Olgulara ait histopatolojik ve klinik veriler hastalara ait patoloji raporlarından elde edildi. E-kaderin, (3-katenin, Siklin Dİ ve c-myc için immünohistokimyasal boyama yöntemi her olguya ait kesitlere uygulandı. Çalışmamızda poliplerde p-kateninin sitoplazmik, nükleer ekspresyonu, Siklin Dİ nükleer ekspresyonu ve E-kaderin ekspresyon kaybının displazi derecesi ile ilişkisi olduğu ve böylece bu moleküllerin adenom-karsinom sekansında baştan beri var olduğunu düşündürdü. Poliplerde P-kateninin nükleer ekspresyonunun invaziv odakları belirlemede yardımcı olabileceği böylece kolorektal tümörleri erken progresyon evresinde yakalamada yararlı olabileceği kanısına varıldı. Kolorektal karsinomlarda P-kateninin sitoplazmik ve nükleer ekspresyonu ile Siklin Dİ 'in nükleer ekspresyonunun karsinogenezısin erken dönemlerinde izlendiği tesbit edildi. İyi diferansiye adenokarsinomlarda Siklin Dİ pozitifliğinin daha belirgin olması, Siklin Dİ 'in iyi prognostik faktörler arasında 72

SUMMARY THE E-CADHERIN, p-CATENIN, c-myc, AND CYCLIN-D1 THAT HAS BEEN SUGGESTED TO HAVE A ROLE IN ADENOMA-CARCINOMA SEQUENCE IN COLON TUMOURS It is reported that, colorectal cancers are the second common cause of cancer related death in western countries. The incidence of the cancer has been increasing. Colorectal polyps are also more common in developed countries particularly in western countries. The most of colorectal carcinomas are developed from adenomatous polyps and this process is known as adenoma-carcinoma sequence. This study was aimed to determine expression and cellular distribution of P-catenin and its relation with E-cadherin in adenoma-carcinoma sequence. We also studied cyclin-Dl and c-myc expression to investigate their possible interaction with cytopasmic and nuclear expression of p-catenin. In general, we aimed to investigate E-cadherin, P-catenin, cyclin-Dl, and c-myc expression patterns in colorectal polyps and tumours in respect to understand their possible roles in adenoma-carcinoma sequence. Following histopathological examination, 60 tumour samples and 3 1 polyp samples were taken from 61 patients diagnosed as colorectal carcinoma and polyp for the study. Immunohistochemical staining of E-cadherin, p-catenin, c-myc and cyclin-D I were performed each section of the cases. In this study, we show that, cytoplasmic and nuclear expression of P-catenin, nuclear expression of cyclin-Dl and decreased expression of E-caderin in polyps could be related with degree of dysplasia, suggesting that tliese proteins may have important roles in adenoma-carcinoma sequence. The nuclear expression of 3- catenin could be useful to detect invasive foci in polyps implicating that, nuclear expression of p-catenin may be used to detection of colorectal tumours in early 74stages. Moreover, the expression of nuclear and cytoplasmic [J-catenin as well as nuclear cyclin-Dl were found in early stages of carcinogenesis. Increased expression of cyclin-Dl in well-differentiated adenocarcinoma suggest that cyclin-Dl could be accounted for good prognosis in such cases. The results also show that, the loss of membrane staining of E-cadherin might be an indicator of worse prognosis in adenoma-carcinoma sequence. The absence of membraneous expression of P-catenin may implicate the development of neoplasm. No specific expression pattern was detected in c-myc expression related to adenoma- carcinoma sequence. Since, c-myc is a target gene of p-catenin, to understand the role of c-myc in Wnt/p-catenin pathway further studies may elucidate complex mechanisms. 75