Abstract 1769
Background
Uveal melanoma is the most common primary cancer of the eye mainly arising from choroid which metastasizes to the liver and frequently leads to death. Till date, there is no current study on the correlation between ATM and BAP1 expression in uveal melanoma. Both proteins trigger DNA damage response (DDR) which leads to DNA repair. Literature reveals that ATM modifies the BAP1for the activation of DNA repair which signifies that there is a connecting link between ATM and BAP1. Therefore, the aim of the study is to detect the co-expression of ATM and BAP1 protein in uveal melanoma patients.
Methods
Sixty-nine formalin fixed paraffin embedded choroidal melanoma samples were taken to evaluate the expression of ATM and BAP1 by immunohistochemistry and validated by western blotting. To check BAP1 mutation, Sanger sequencing was done on control and UM samples. Results were then correlated with clinical and histopathological parameters. To determine the prognostic significance, Kaplan–Meier analysis and multivariate analysis by Cox’s Proportional Hazards Model was performed.
Results
There was a male preponderance in our study. Histopathological high-risk factors were identified in 48% cases. Both ATM and BAP1 show loss of nuclear expression in 55% of the cases and this was statistically significant with high pigmentation, LTD >10mm, TIL and cell type (p < 0.05). On multivariate analysis, advanced tumour staging and epithelioid cell type are found to be independent prognostic factors.
Conclusions
Our data suggest that loss of nATM and nBAP1might serve as a potential prognostic marker in the pathogenesis of uveal melanoma leading to increased risk of metastasis. These findings demonstrate the synergistic role of ATM and BAP1 proteins and may have a therapeutic potential in uveal melanoma. However, further studies are required in a larger cohort of patients with longer follow up and translational validation needs to be performed.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5729 - Expression of mutant p53 affects cancer cell sensitivity to topotecan
Presenter: Rimma Mingaleeva
Session: Poster Display session 1
Resources:
Abstract
5725 - Breast cancer organoids a new tool for the prediction of drugs penetration and patient’outcome
Presenter: Giuseppina Roscigno
Session: Poster Display session 1
Resources:
Abstract
5680 - Aptamer-mediated exosomes detection for early breast cancer identification.
Presenter: Cristina Quintavalle
Session: Poster Display session 1
Resources:
Abstract
2460 - MicroRNA-181c promotes tamoxifen resistance in breast cancer cells via upregulation Akt/mTOR axis
Presenter: Alexander Scherbakov
Session: Poster Display session 1
Resources:
Abstract
3751 - Spatio-temporal separation of tumor infiltrating CD8+ T-cells and HER2/neu+ tumor cells in tumor-immune milieu of infiltrating ductal carcinoma of the breast
Presenter: Sandhya Sreedharan
Session: Poster Display session 1
Resources:
Abstract
4664 - Large genomic rearrangements in BRCA1 and BRCA2 genes in the Portuguese population.
Presenter: Joao Pinto
Session: Poster Display session 1
Resources:
Abstract
4611 - Non-BRCA1/2 hereditary breast and ovarian cancer: findings from a multidisciplinary program
Presenter: Ana Monteiro
Session: Poster Display session 1
Resources:
Abstract
5340 - Quantitative imaging and characterization of collagen patterns in high grade serous ovarian carcinoma (HGSOC)
Presenter: Ruby Huang
Session: Poster Display session 1
Resources:
Abstract
4209 - Semiquantitative assessment of vimentin expression in prostate cancer (PC)
Presenter: Marina Puchinskaya
Session: Poster Display session 1
Resources:
Abstract
3309 - Heat Shock Protein 90 chaperones and Protein Kinase D3 regulates androgen-independent prostate cancer development
Presenter: Attila Varga
Session: Poster Display session 1
Resources:
Abstract