Assessment of Tissue Expression of PIR2/Rnf144b Protein in the Different Stages of Endometrial Cancer

Abstract

ndometrial carcinoma most frequently occurs in women within the sixth and seventh decades of life, at a median age of 60 years. The RING finger motif, present in several functionally different proteins, was first recognized in the protein encoded by the Very Interesting New Gene 1. in the early 1990s. Eight metal-binding residues that organize two zinc atoms in an interleaved pattern for folding and biological actions are found in the RING finger domain. By mediating various protein-protein interactions, RING finger proteins work and one of their key biological functions is catalyzing ubiquitylation which is a controlled mechanism by which ubiquitin is covalently bound to other proteins, a strongly preserved 76-amino acid polypeptide. Three classes of enzymes are involved in this modification: the ubiquitin-activating enzyme (E1), the ubiquitin-conjugating enzyme (E2) and the ubiquitin-protein isopeptide ligase (E3). E3 is mainly responsible for determination of the specificity for ubiquitin conjugation PIR2/RNF144B (PIR2) is an E3- ubiquitin ligase that is essential for the apoptosis regulation and cell proliferation. PIR2 protein stability is associated, mainly with the modulation of GSK3β activity. PIR2 protein is not expressed in normal endometrium, but expressed only in EC. In EC cell lines, PIR2 drives cell proliferation when estrogen-mediated growth signaling is lost. Recent in vivo study, which has been done on endometrial cancer cell lines, suggested that PIR2 can potentially be used as a biomarker for endometrial cancer. So, we conducted this retrospective cohort study to assess tissue expression of PIR2 protein in the different stages of endometrial cancer on 60 women diagnosed as endometrial cancer subdivided into 1st group included 30 patients with stage 1 endometrial cancer by surgical staging and 2nd group included 30 patients with other advanced stages of endometrial cancer by surgical staging in Ain Shams University Maternity Hospital (The Early Cancer Detection Unit). Our results showed that, No significant association was detected between the PIR2/RNF144B protein expression in different histopathological subgroups (F=1.23, p>0.05). This study revealed a high significant difference in the percentage of cells expressing the PIR2/RNF144B protein and the histopathological grade (p-value: 0.003), higher tumor grades are associated with large number of positive cells. In addition, a high statistically significant difference was detected between grade I tumors vs grade IV (p-value <0.01), however a moderated significant difference was reached between grade I versus grade III (p-value: 0.03) and between grade II and IV (p-value: 0.04).