TY  - JOUR
AU  - Milovanović, Jelena
AU  - Todorović-Raković, Nataša
AU  - Vujasinović, Tijana
AU  - Greenman, John
AU  - Mandušić, Vesna
AU  - Radulović, Marko
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10392
AB  - Background Granulysin (GNLY) is a cytolytic and proinflammatory molecule which also acts as an immune alarmin. The multifunctional nature of this molecule has made it challenging to define its full potential as a biomarker in breast cancer.AimTo evaluate the prognostic value of intratumoral GNLY in primary breast cancer patients and its association with established clinicopathological parameters.Patients and methodsThe study included 69 node-negative breast cancer patients with known clinicopathological parameters, all of whom had not received any prior hormonal or chemotherapeutic systemic therapy that would interfere with the course of disease. The median follow-up period was 144 months. Steroid hormone receptor status was determined by ligand-binding assay and HER2 status by chromogenic in situ hybridisation (CISH). Intratumoral GNLY mRNA levels were determined by RT-qPCR. Prognostic performance was evaluated by the receiver operating characteristic (ROC), Cox proportional hazards regression and Kaplan-Meier analysis. Classification of patients into GNLYlow and GNLYhigh subgroups was performed by the use of the outcome-oriented cut-off point categorisation approach.ResultsThere was a significant difference between GNLY values of patients without any recurrences and those with local or distant recurrences (Mann-Whitney test, p = 0.05 and p = 0.02, respectively). None of the tested parameters showed prognostic significance for local and distant recurrences when combined. When distant metastases and local recurrences were separated as events, the best prognostic performance was observed for GNLY as compared with any clinicopathological parameter (AUC=0.24 and p = 0.04 for local events; AUC=0.71 and p = 0.03 for distant events). Local recurrence incidence was 0% for the GNLYhigh subgroup and 19% for the GNLYlow subgroup; however distant recurrence incidence was 24% for the GNLYhigh subgroup but only 3% for the GNLYlow subgroup (Kaplan–Meier analysis). A significant positive correlation was found between intratumoral ER and GNLY levels, and a significant negative correlation between tumour grade and GNLY levels.ConclusionHigh levels of granulysin prognosticate low risk of local recurrence but a high risk of distant metastasis in primary, untreated, breast cancer patients.
T2  - Pathology - Research and Practice
T1  - Can granulysin provide prognostic value in primary breast cancer?
VL  - 237
SP  - 154039
DO  - 10.1016/j.prp.2022.154039
ER  - 

@article{
author = "Milovanović, Jelena and Todorović-Raković, Nataša and Vujasinović, Tijana and Greenman, John and Mandušić, Vesna and Radulović, Marko",
year = "2022",
abstract = "Background Granulysin (GNLY) is a cytolytic and proinflammatory molecule which also acts as an immune alarmin. The multifunctional nature of this molecule has made it challenging to define its full potential as a biomarker in breast cancer.AimTo evaluate the prognostic value of intratumoral GNLY in primary breast cancer patients and its association with established clinicopathological parameters.Patients and methodsThe study included 69 node-negative breast cancer patients with known clinicopathological parameters, all of whom had not received any prior hormonal or chemotherapeutic systemic therapy that would interfere with the course of disease. The median follow-up period was 144 months. Steroid hormone receptor status was determined by ligand-binding assay and HER2 status by chromogenic in situ hybridisation (CISH). Intratumoral GNLY mRNA levels were determined by RT-qPCR. Prognostic performance was evaluated by the receiver operating characteristic (ROC), Cox proportional hazards regression and Kaplan-Meier analysis. Classification of patients into GNLYlow and GNLYhigh subgroups was performed by the use of the outcome-oriented cut-off point categorisation approach.ResultsThere was a significant difference between GNLY values of patients without any recurrences and those with local or distant recurrences (Mann-Whitney test, p = 0.05 and p = 0.02, respectively). None of the tested parameters showed prognostic significance for local and distant recurrences when combined. When distant metastases and local recurrences were separated as events, the best prognostic performance was observed for GNLY as compared with any clinicopathological parameter (AUC=0.24 and p = 0.04 for local events; AUC=0.71 and p = 0.03 for distant events). Local recurrence incidence was 0% for the GNLYhigh subgroup and 19% for the GNLYlow subgroup; however distant recurrence incidence was 24% for the GNLYhigh subgroup but only 3% for the GNLYlow subgroup (Kaplan–Meier analysis). A significant positive correlation was found between intratumoral ER and GNLY levels, and a significant negative correlation between tumour grade and GNLY levels.ConclusionHigh levels of granulysin prognosticate low risk of local recurrence but a high risk of distant metastasis in primary, untreated, breast cancer patients.",
journal = "Pathology - Research and Practice",
title = "Can granulysin provide prognostic value in primary breast cancer?",
volume = "237",
pages = "154039",
doi = "10.1016/j.prp.2022.154039"
}

Milovanović, J., Todorović-Raković, N., Vujasinović, T., Greenman, J., Mandušić, V.,& Radulović, M.. (2022). Can granulysin provide prognostic value in primary breast cancer?. in Pathology - Research and Practice, 237, 154039.
https://doi.org/10.1016/j.prp.2022.154039

Milovanović J, Todorović-Raković N, Vujasinović T, Greenman J, Mandušić V, Radulović M. Can granulysin provide prognostic value in primary breast cancer?. in Pathology - Research and Practice. 2022;237:154039.
doi:10.1016/j.prp.2022.154039 .

Milovanović, Jelena, Todorović-Raković, Nataša, Vujasinović, Tijana, Greenman, John, Mandušić, Vesna, Radulović, Marko, "Can granulysin provide prognostic value in primary breast cancer?" in Pathology - Research and Practice, 237 (2022):154039,
https://doi.org/10.1016/j.prp.2022.154039 . .