The frequencies of micronuclei, nucleoplasmic bridges and nuclear buds as biomarkers of genomic instability in patients with urothelial cell carcinoma

Arjeta Podrimaj-Bytyqi,Ana Borovečki,Isa R Elezaj,Qerim Selimi,Goneta Gashi,Suzana Manxhuka-Kerliu

doi:10.1038/s41598-018-35903-5

Arjeta Podrimaj-Bytyqi, Ana Borovečki + Show 4 more

Open Access

https://doi.org/10.1038/s41598-018-35903-5

Copy DOI

Journal: Scientific Reports	Publication Date: Dec 1, 2018
Citations: 22	License type: open-access

Affiliation: University of Zagreb, University of Prishtina

Abstract

Bladder urothelial cell carcinoma (UCC) is an increasingly prevalent cancer worldwide, and thus, gaining a better understanding of its identifiable risk factors is a global priority. This study addressed this public health need with the understanding that cancer-initiating events, such as chromosome breakage, loss and rearrangement, can be reasonably used as biomarkers to evaluate an individual’s cancer risk. Overall, forty bladder cancer patients and twenty controls were evaluated for genomic instability. To the best of the investigators’ knowledge, this is the first study to perform micronucleus (MN) assays simultaneously in urothelial exfoliated cells (UEC), buccal exfoliated cells (BEC), and peripheral blood lymphocytes (PBL) in first-diagnosed, non-smoker bladder UCC patients. Additionally, the frequency of nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in PBL was evaluated. The MN frequencies in UEC, BEC, and PBL, as well as the frequencies of NPBs and NBUDs, were significantly higher in patients than in controls. In conclusion, MN assays, particularly in UEC, may be used to identify individuals who are at high risk of developing UCC, as single or as additional triage test to UroVysion FISH test. Our results further validate the efficacy of biomarkers, such as MN, NPBs, and NBUDs, as predictors of genomic instability.

Highlights

Bladder urothelial cell carcinoma (UCC) has become a globally common cancer, with an estimated 430000 new cases diagnosed in 2012, and it has a higher incidence rate in men than in women[1] and increased frequency in industrial areas[2] and in people exposed to arsenic[3], cigarette smoking, alcohol, and so on[4]
When MNi in urothelial exfoliated cells (UEC), buccal exfoliated cells (BEC) and peripheral blood lymphocytes (PBL), as well as nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs), were correlated to the tumour stage and the tumour recurrences, we found that among all of these variables, only the MN frequency in PBL showed a positive trend of correlation with the tumour stage, but it did not reach the level of statistical significance
We used the MN assay in UEC and BEC and the cytokinesis-block micronucleus (CBMN) cytome assay in PBL to evaluate genomic instability in bladder UCC patients

Summary

Introduction

Bladder urothelial cell carcinoma (UCC) has become a globally common cancer, with an estimated 430000 new cases diagnosed in 2012, and it has a higher incidence rate in men than in women[1] and increased frequency in industrial areas[2] and in people exposed to arsenic[3], cigarette smoking, alcohol, and so on[4]. Some of one or more of the cell’s protective mechanisms are disrupted, and the cell’s genomic integrity is compromised[9]. Chromosomal instability (CIN) is a hallmark cause of the aneuploidy that is observed in most solid tumour cells and is often associated with the missegregation of chromosomes that results from improper kinetochore-microtubule attachments and the consequent presence of lagging chromosomes during anaphase[10,11,12]. Covariates Number NMIUC MIUC Age range Smoking status T stage Ta T1 T2 T3 T4 Tis Tx Grading (WHO 2004)* Low grade High grade Recurrence Recurrent Non-recurrent. Non-muscle invasive urothelial carcinoma; MIUC- Muscle invasive urothelial carcinoma. *For reference see: Eble JN et al Pathology and genetics of tumors of the urinary system and male genital organs, (2004)

Objectives

Methods

Results

Conclusion