Expression of MLH1, PMS2, MSH2, MSH6, p53 in different stages of Barrett's esophagus development from metaplasia to esophageal adenocarcinoma

Cilj istraživanja je analiza gubitka ekspresije proteina sustava popravka pogrešno sparenih baza u metaplazija-displazija-adenokarcinom slijedu Barrett jednjaka. Retrospektivno su analizirani podaci za 70 pacijenata sa patohistološkom dijagnozom Barrett jednjaka ili adenokarcinoma jednjaka sa Kliničkog Zavoda za Patologiju i Citologiju Kliničkog bolničkog centra Zagreb u periodu od siječnja 2009 do siječnja 2011. Pacijenti su bili podijeljeni u tri skupine: BE bez displazije (22 pacijenta), BE sa displazijom (37 pacijenata) te adenokarcinom (11 pacijenata). Imunohistokemijska ekspresija MLH1, MSH2, PMS2 i MSH6 MMR sustava je izmjerena i uspoređena sa ekspresijom tumor proteina p53. Gubitak ekspresije MLH1 je uočen kod 81,8% pacijenata sa karcinom, 34,4% sa displazijom te 50% bez displazije. Gubitak ekspresije PMS2 je uočen kod 81,8% pacijenata sa karcinomom, 35,1% sa displazijom te 54,5% pacijenata bez displazije. 18,2% pacijenata bez displazije je imalo gubitak ekspresije MSH2 te MSH6, dok ni jedan pacijent sa karcinomom ili sa displazijom nije imao gubitak ekspresije navedenih proteina. Uočena je pozitivna korelacija između MLH1 i PMS2 ekspresije (Spearman ρ 0.97; P < 0.001) te između MSH2 i MSH6 ekspresije (Spearman ρ 0.90, P < 0.001) u cijelom uzorku te svakoj pojedinačnoj grupi. Nije uočena značajna korelacija MLH1 i PMS2 sa p53 ekspresijom, osim u grupi pacijenata sa displazijom (φ 0.402, P = 0.030 for MSH1; φ 0.371, P = 0.042 for PMS2). Iako smo pokazali značajan gubitak ekspresije MLH1 i PMS2 u BE metaplazija – karcinoma slijedu, zbog retrospektivnog dizajna studije i niskog broja pacijenata ne možemo zaključiti da se trenutno MLH1 i PMS 2 mogu upotrebljavati kao biomarkeri u praćenju pacijenata ili odluci o daljnjem liječenju.Aim of this study was to analyze the loss of mismatch repair (MMR) system protein expression in metaplasia-dysplasia-adenocarcinoma sequence of Barrett esophagus (BE). This study retrospectively analyzed the data from 70 patients with pathohistological diagnosis of BE or esophageal adenocarcinoma (EAC) treated at the Clinical Department of Pathology and Cytology, University Hospital Center Zagreb, from January 2009 to January 2011. Patients were divided into three groups: BE without dysplasia (22 patients), BE with dysplasia (37 patients), and EAC (11 patients). Immunohistochemical expression of MutL homologue 1 (MLH1), MutS homologue 2 (MSH2), postmeiotic segregation increased 2 (PMS2), and MutS homologue 6 (MSH6) of DNA MMR system was measured and compared with tumor protein p53 expression. Total of 81.8% and 81.8% patients with EAC, 32.4% and 35.1% patients with dysplasia, and 50% and 54.5% patients without dysplasia had loss of MLH1 and PMS2 expression, respectively. Patients with EAC and patients with dysplasia did not have loss of MSH2 and MSH6 expression, and 18.2% patients without dysplasia had loss of MSH2 and MSH6 expression. There was a strong positive correlation between MLH1 and PMS2 expression (Spearman ρ 0.97; P < 0.001) and between MSH2 and MSH6 expression (Spearman ρ 0.90, P < 0.001) in the entire sample and in all BE groups. No significant correlations of MLH1 and PMS2 with p53 expression were found, except in dysplasia group (φ 0.402, P = 0.030 for MSH1; φ 0.371, P = 0.042 for PMS2). Although we demonstrated considerable loss of MLH1 and PMS2 expression in BEassociated carcinoma sequence, due to the retrospective study design and low number of patients we cannot conclude that MLH1 and PMS2 can be used as biomarkers for patient surveillance and therapy-making decisions