JBUON 2020; 25(3): 1482-1489 ISSN: 1107-0625, online ISSN: 2241-6293 • www.jbuon.com Email: editorial_ofce@jbuon.com ORIGINAL ARTICLE Corresponding author: Hariklia Gakiopoulou, MD,PhD. 1 st Department of Pathology, School of Medicine, The National and Ka- podistrian University of Athens, Greece, 75 Mikras Asias Str, Goudi, 11527, Athens, Greece. Tel: +30 210 7462170, Email: charagak28@gmail.com, chgakiop@med.uoa.gr Received: 20/10/2019; Accepted: 15/11/2019 Replication Protein A (RPA1, RPA2 and RPA3) expression in gastric cancer: correlation with clinicopathologic parameters and patients’ survival Ef Fourtziala 1 , Nick Givalos 2 , Nikolaos Alexakis 3 , John Griniatsos 4 , Nektarios Alevizopoulos 5 , Nikolaos Kavantzas 1 , Andreas C Lazaris 1 , Penelope Korkolopoulou 1 , Hariklia Gakiopoulou 1 1 1 st Department of Pathology, School of Medicine, The National and Kapodistrian University of Athens, Greece. 2 2 nd Department of General Surgery, General Hospital of Attica “KAT”, Athens, Greece. 3 1 st First Department of Propaedeutic Surgery, The National and Kapodistrian University of Athens, Hippocratio Hospital, Athens, Greece. 4 1 st Department of Surgery, Medical School, The National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece. 5 Department of Oncology, Evangelismos General Hospital, Athens, Greece. Summary Purpose: Replication Protein A (RPA) consists of three subu- nits (RPA1, RPA2 and RPA3) essential for all major DNA metabolic pathways. Although RPA seems to be a promis- ing therapeutic target, its role in human cancers has not been fully elucidated. This is the frst study investigating the expression of all the three RPA subunits in a series of 74 resected gastric carcinomas and analyzing the possible correlations with clinicopathologic parameters (histological type, grade, lymphovascular invasion, lymph node status and disease stage), Ki-67 proliferative index, Topoisomerase IIa expression and patients’ survival. Methods: Immunohistochemistry using monoclonal anti- bodies. Univariate and multivariate statistical analysis. Results: All the three subunits showed widespread nuclear expressions in gastric carcinomas with signifcant associa- tions among their expressions. RPA2 demonstrated higher expression levels in low grade carcinomas and a gradual signifcant decrease from N0 to N3 and from stage I to stage IV carcinomas. All the three subunits were statistical signif- cantly more abundant in lymph node negative and earlier stage (stage I & II) gastric carcinomas. No associations were established among RPAs and the proliferative marker Ki-67. In patients with positive lymph nodes and advanced tumor stage, RPA1 expression seemed to predict a better overall survival implying a probable predictive role. Conclusions: The widespread expression of RPA(1-3) sug- gests one or more roles in gastric cancer. Their presence in earlier stage tumors probably ofers an opportunity for early targeted therapy. Their probable predictive value in node pos- itive and advanced stage tumors needs further investigation with respect to specifc chemotherapeutic treatments. Key words: gastric cancer, Replication Protein A (1-3), sur- vival Introduction Replication protein A (RPA) is the major single- strand DNA (ssDNA) binding complex in eukaryotes [1]. RPA is essential for all major DNA metabolic pathways, including DNA replication, repair, recom- bination, cell cycle progression, and the DNA dam- age response, playing a role as a sensor in multiple DNA checkpoint pathways [1-5]. RPA is required for each of the four major DNA repair pathways: nucleotide excision repair (NER), base excision re- pair (BER), DNA mismatch repair (MMR), and DNA double strand break (DSB) repair [1]. Human RPA is present in cells as a heterotrimeric complex consist- This work by JBUON is licensed under a Creative Commons Attribution 4.0 International License.