title: Prognostic role of NF-YA splicing isoforms and Lamin A status in low grade endometrial cancer.
abstract: Although most cases of low grade (G1) endometrial cancer (EC) do not behave aggressively, in rare instances, can progress in a highly aggressive manner. In this study we analyzed formalin-fixed, paraffin-embedded (FFPE) EC tissues to find novel clinical and biological features to help diagnosis and treatment of G1 ECs s in order to better stratify patient risk of recurrence. A retrospective cohort of FFPE specimens from patients with EC (n=87) and benign tissue specimens (NE) from patients who underwent a hysterectomy to treat other benign disease (n = 13) were collected. Total RNA and proteins were extracted and analyzed, respectively, by quantitative PCR and western blotting. NF-YAs is expressed and lamin A is down-modulated in all high grade (G2 and G3) ECs. In G1 ECs, NF-YAs expression is heterogeneous being expressed only in a subset of these tumours. Interestingly, the G1 ECs that express NF-YAs display low levels of lamin A similar to those present in G2 and G3 ECs. Of note, this pattern of NF-YAs and lamin A expression correlates with tumor aggressiveness assessed by comparative analysis with estrogen receptor (ER) status and epithelial-mesenchymal transition (EMT) markers thus suggesting its potential role as biomarker of tumour aggressiveness in G1 EC. In all grade ECs, lamin A is strongly downmodulated, being its expression inversely correlated with tumor aggressiveness and its loss of expression. We identified NF-YAs and lamin A expression levels as novel potential biomarkers useful to identify G1 ECs patients with risk of recurrence.
authors.affiliation: Department of Research, Advanced Diagnostics and Technological Innovation, Area of Translational Research, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Cicchillitti
authors.affiliation: Department of Experimental Clinical Oncology, Gynecologic Oncology Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Corrado
authors.affiliation: Department of Research, Advanced Diagnostics and Technological Innovation, Anatomy Pathology Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Mariantonia
authors.initials: M
authors.lastname: Carosi
authors.affiliation: Department of Research, Advanced Diagnostics and Technological Innovation, Anatomy Pathology Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Malgorzata Ewa
authors.initials: ME
authors.lastname: Dabrowska
authors.affiliation: Department of Research, Advanced Diagnostics and Technological Innovation, Area of Translational Research, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Loria
authors.affiliation: Department of Research, Advanced Diagnostics and Technological Innovation, Area of Translational Research, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Falcioni
authors.affiliation: Department of Experimental Clinical Oncology, Gynecologic Oncology Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cutillo
authors.affiliation: Department of Research, Advanced Diagnostics and Technological Innovation, Area of Translational Research, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Piaggio
authors.affiliation: Department of Experimental Clinical Oncology, Gynecologic Oncology Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Vizza
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D023081:CCAAT-Binding Factor / Q000032:analysis* / Q000235:genetics; D016889:Endometrial Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007044:Hysterectomy; D034904:Lamin Type A / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D060787:Neoplasm Grading; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D023081:CCAAT-Binding Factor; D034904:Lamin Type A; C492061:NFYA protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D011960:Receptors, Estrogen
keywords: NF-Y; endometrial cancer; estrogen receptor; lamin A; miR-200 family