Rectum cancers with distant metastases (Stage IV) show decreased tissue expression of E cadherin at the invasive tumor front

Aim: Rectal cancers (RC) are one of the most cause of death worldwide. Survival of patients is mainly associated with the TNM stage. However, patients characterized by the same tumor stage often have prominent distinct survival. This is particularly a clinical challenge and new biomarkers are needed. In the present research, we analyzed the prognostic role of E-cadherin (EC) in stage IV RC. Methods: Eighty-five stage IV RC patients who underwent surgery at Kirikkale University during 2001–2015 were included in this retrospective study. EC was scored on immunohistochemical (IHC) stained sections with a cut-off value of ≥50% ratio. The relationship between the results and the clinicopathological characteristics was analyzed. Results : EC percentage was significantly downregulated in RCs classified as advanced pT ( p=  0.005) , angiolymphatic invasion ( p=  0.034), advanced stage ( p = 0.006 ), high number of metastatic lymph nodes ( p =0.039) and high grade (p=0.014). In univariate analysis, low EC patients had worse 5-year survival (RFS: 28.3%, p<0.001; OS: 41.2%, p<0.001). Multivariate analyzes confirmed that low EC is an independent worse survival parameter for RFS (Hazard ratio [HR]: 1.33 [1.15-3.46], p=0.001 ) and OS (HR: 1.57 [1.09–4.32], p=0.002). Conclusions: Our study confirmed the prognostic significance of low EC in stage IV RCs. Therefore, we suggest that this parameter may be an indicator of worse prognosis in RCs. This biomarker can be defined on IHC stained slides readily and can use a molecular agent in RC therapy . Keywords: E cadherin, rectal cancer , prognostic markers, stage IV Ozet Amac: Rektal kanserler (RK) dunya genelinde en onemli olum nedenlerinden biridir. Hastalarin sagkalimi temel olarak TNM evresi ile iliskilidir . Bununla birlikte, ayni tumor evresi ile karakterize edilen hastalar siklikla belirgin farkli sag kalimlara sahiptir. Bu ozellikle klinik bir celiskidir ve yuksek riskli hastalari ayirt etmek icin yeni biobelirteclere ihtiyac vardir. Bu arastirmada, stage IV RK'da E cadherin (EC) 'nin sag kalimdaki rolunu analiz ettik. Yontem: Bu retrospektif calismaya Kirikkale Universitesi'nde 2001-2015 arasinda cerrahi girisim uygulanan seksen bes RK hastasi dahil edildi. EC, immunohistokimyasal (IHK) boyanmis kesitler uzerinde %50 sinir degeri olarak skorlandi. Sonuclar ve klinikopatolojik ozellikler arasindaki iliski analiz edildi. Bulgular: EC yuzdesi, ileri pT (p = 0.005), anjiyolenfatik invazyon (p = 0.034), ileri evre (p=0.006), yuksek lenf nodu metastazi sayisi (p=0.039) ve ileri grade (p=0.014) olan RK'larda anlamli derecede dusuktu. Tek degiskenli analizde, dusuk EC’li hastalar 5 yillik kotu sagkalima sahipti (RFS:% 28.3, p <0.001; OS:% 41.2, p<0.001). Cok degiskenli analizler, dusuk EC'nin RFS ( Hazard ratio [HR]: 1.33 [1.15 – 3.46], p = 0.001) ve OS (HR: 1.57 [1.09 – 4.32], p=0.002) icin bagimsiz bir kotu hayatta kalma parametresi oldugunu dogruladi. Sonuc: Sonuclarimiz stage IV RK'larda dusuk EC' nin prognostik onemini dogruladi. Bu nedenle, bu parametrenin RK'larda kotu prognozun bir gostergesi olabilecegini oneriyoruz. Bu biyobelirtec, IHK boyali lamlar uzerinde kolaylikla tanimlanabilir ve RK tedavisinde bir molekuler ajan olarak kullanilabilir. Anahtar Sozcukler: E cadherin, rektal kanser, prognostik belirtecler, stage IV