TY  - CONF
AU  - Kožik, Bojana
AU  - Todorović, Lidija
AU  - Božović, Ana
AU  - Kolaković, Ana
AU  - Vasiljević, Tijana
AU  - Đurić, Mladen
AU  - Đermanović, Aleksandar
AU  - Mandušić, Vesna
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/13104
AB  - Introduction: Venous invasion has consistently been shown to be associated with poor prognosis in rectal carcinoma (RC), both when detected by pathology and radiology. Extramural venous invasion (EMVI) is characterized by the presence of tumor cells within veins outside the bowel wall and is strongly associated with poor survival and increased risk of local recurrence and distant metastases. Molecular basis of EMVI is still unexplored and genes that regulate tumor microenvironment interactions may have significant role in this process. ZEB1 is transcriptional factor that promote cancerogenesis by indirect regulation of epithelial-mesenchymal transition (EMT) process, while LOXL2 contributes to tumor invasion and metastasis due to its role in the stabilization of the extracellular matrix. Aim: This study aimed to compare the expression level of ZEB1 and LOXL2 genes in relation to EMVI status and other clinic-pathological parameters of RC patients. Methods: We conducted preliminary study on 21 untreated RC patients (9 EMVI+ and 11 EMVI- ) who underwent curative resection in 2016-2018 at Oncology Institute of Vojvodina. The presence of EMVI was assessed on standard hematoxylin and eosin-stained histolological sections of postoperative tumor specimen samples, from which RNA was isolated. Expression of ZEB1 and LOXL2 mRNA was measured using quantitative real-time PCR. Results: Comparative analysis revealed higher expression level of ZEB1 in EMVI positive samples and in patients in TNMIII stage, however the observed differences had no statistic significance (p=0.323 and p=0.197, respectively). Significant difference in LOXL2 expression according to the EMVI status was not detected (p=0.915), while we noted higher LOXL2 expression in late stages of disease, but without statistic significance (p=0.342). Relative expression of these two genes was not associated with metastases frequency and death outcome. Conclusion: Further analyses on larger number of samples with more potential molecular targets included are required and planed.
AB  - Uvod: Venska invazija je kontinuirano asocirana sa lošom prognozom kod obolelih od karcinoma rektuma (KR), bilo da je detektovana patološkim ili radiološkim metodama. Ekstramuralna venska invazija (EMVI) se karakteriše kao prisustvo tumorskih ćelija u venskim sudovima izvan zida debelog creva koje je značajno asocirano sa lošim preživljavanjem i povećanim rizikom za nastanak lokalnih recidiva i udaljenih metastaza. Molekularna osnova EMVI procesa nije dovoljno ispitana, a geni koji regulišu interakcije u tumorskoj mikrosredini mogu imati potencijalnu ulogu. ZEB1 je transkripcioni factor koji stimuliše kancerogenezu indirektnom regulacijom epitelnomezenhimske tranzicije (EMT), dok LOXL2 doprinosi procesu tumorske invazije ulogom u stabilizaciji ektracelularnog matriksa. Cilj: Cilj ove studije je uporediti relativnu ekspresije gena ZEB1 i LOXL2 u odnosu na EMVI status i druge kliničko-patološke parametre KR pacijenta. Metode: Ova preliminarna studija obuhvatila je 21 netretiranih KR pacijenata (9 EMVI+ i 11 EMVI-) koji su lečeni operativnim putem u periodu 2016-2018. god. u Institutu za onkologiju Vojvodina. Prisustvo EMVI je utvrđeno na standardno hematoksilinom i eozinom bojenim isečcima postoperativnog tumorskog tkiva iz kojih je izolovana RNK. Ekspresija ZEB1 i LOXL2 iRNA izmerena je kvantitativnom PCR metodom u realnom vremenu. Rezultati: Uporednom analizom uočena je povišena ekspresija ZEB1 kod EMVI+ uzoraka i kod obolelih u TNMIII stadijumu, ali uočene razlike nisu bile statistički značajne (p=0,323 i p=0,197, respektivno). Znčajna razlika u ekspresiji LOXL2 u odnosu na EMVI status nije detektovana (p=0,915), a zabeležena je i povećana ekspresija LOXL2 u kasnim stadijumima bolesti, ali bez statističke značajnosti (p=0,342). Relativna ekspresija ova dva gena nije značajno povezana sa pojavom metstaza i krajnjim ishodom bolesti. Zaključak: Dalje analize na većem broju uzoraka sa više uključenih molekularnih targeta u studiju su neophodne i planirane u budućnosti.
PB  - Belgrade : Serbian Medical Society Oncology Section
C3  - Anali kancerološke sekcije SLD : 60. Kancerološka nedelja : Knjiga apstrakata
T1  - Expression of ZEB1 and LOXL2 in rectal carcinoma and their correlation with extramural venous invasion (EMVI): preliminary study
T1  - Ekspresija ZEB1 i LOXL2 gena kod karcinoma rektuma i njihova korelacija sa ekstramuralnom venskom invazijom (EMVI): preliminarna studija
UR  - https://hdl.handle.net/21.15107/rcub_vinar_13104
ER  - 

@conference{
author = "Kožik, Bojana and Todorović, Lidija and Božović, Ana and Kolaković, Ana and Vasiljević, Tijana and Đurić, Mladen and Đermanović, Aleksandar and Mandušić, Vesna",
year = "2023",
abstract = "Introduction: Venous invasion has consistently been shown to be associated with poor prognosis in rectal carcinoma (RC), both when detected by pathology and radiology. Extramural venous invasion (EMVI) is characterized by the presence of tumor cells within veins outside the bowel wall and is strongly associated with poor survival and increased risk of local recurrence and distant metastases. Molecular basis of EMVI is still unexplored and genes that regulate tumor microenvironment interactions may have significant role in this process. ZEB1 is transcriptional factor that promote cancerogenesis by indirect regulation of epithelial-mesenchymal transition (EMT) process, while LOXL2 contributes to tumor invasion and metastasis due to its role in the stabilization of the extracellular matrix. Aim: This study aimed to compare the expression level of ZEB1 and LOXL2 genes in relation to EMVI status and other clinic-pathological parameters of RC patients. Methods: We conducted preliminary study on 21 untreated RC patients (9 EMVI+ and 11 EMVI- ) who underwent curative resection in 2016-2018 at Oncology Institute of Vojvodina. The presence of EMVI was assessed on standard hematoxylin and eosin-stained histolological sections of postoperative tumor specimen samples, from which RNA was isolated. Expression of ZEB1 and LOXL2 mRNA was measured using quantitative real-time PCR. Results: Comparative analysis revealed higher expression level of ZEB1 in EMVI positive samples and in patients in TNMIII stage, however the observed differences had no statistic significance (p=0.323 and p=0.197, respectively). Significant difference in LOXL2 expression according to the EMVI status was not detected (p=0.915), while we noted higher LOXL2 expression in late stages of disease, but without statistic significance (p=0.342). Relative expression of these two genes was not associated with metastases frequency and death outcome. Conclusion: Further analyses on larger number of samples with more potential molecular targets included are required and planed., Uvod: Venska invazija je kontinuirano asocirana sa lošom prognozom kod obolelih od karcinoma rektuma (KR), bilo da je detektovana patološkim ili radiološkim metodama. Ekstramuralna venska invazija (EMVI) se karakteriše kao prisustvo tumorskih ćelija u venskim sudovima izvan zida debelog creva koje je značajno asocirano sa lošim preživljavanjem i povećanim rizikom za nastanak lokalnih recidiva i udaljenih metastaza. Molekularna osnova EMVI procesa nije dovoljno ispitana, a geni koji regulišu interakcije u tumorskoj mikrosredini mogu imati potencijalnu ulogu. ZEB1 je transkripcioni factor koji stimuliše kancerogenezu indirektnom regulacijom epitelnomezenhimske tranzicije (EMT), dok LOXL2 doprinosi procesu tumorske invazije ulogom u stabilizaciji ektracelularnog matriksa. Cilj: Cilj ove studije je uporediti relativnu ekspresije gena ZEB1 i LOXL2 u odnosu na EMVI status i druge kliničko-patološke parametre KR pacijenta. Metode: Ova preliminarna studija obuhvatila je 21 netretiranih KR pacijenata (9 EMVI+ i 11 EMVI-) koji su lečeni operativnim putem u periodu 2016-2018. god. u Institutu za onkologiju Vojvodina. Prisustvo EMVI je utvrđeno na standardno hematoksilinom i eozinom bojenim isečcima postoperativnog tumorskog tkiva iz kojih je izolovana RNK. Ekspresija ZEB1 i LOXL2 iRNA izmerena je kvantitativnom PCR metodom u realnom vremenu. Rezultati: Uporednom analizom uočena je povišena ekspresija ZEB1 kod EMVI+ uzoraka i kod obolelih u TNMIII stadijumu, ali uočene razlike nisu bile statistički značajne (p=0,323 i p=0,197, respektivno). Znčajna razlika u ekspresiji LOXL2 u odnosu na EMVI status nije detektovana (p=0,915), a zabeležena je i povećana ekspresija LOXL2 u kasnim stadijumima bolesti, ali bez statističke značajnosti (p=0,342). Relativna ekspresija ova dva gena nije značajno povezana sa pojavom metstaza i krajnjim ishodom bolesti. Zaključak: Dalje analize na većem broju uzoraka sa više uključenih molekularnih targeta u studiju su neophodne i planirane u budućnosti.",
publisher = "Belgrade : Serbian Medical Society Oncology Section",
journal = "Anali kancerološke sekcije SLD : 60. Kancerološka nedelja : Knjiga apstrakata",
title = "Expression of ZEB1 and LOXL2 in rectal carcinoma and their correlation with extramural venous invasion (EMVI): preliminary study, Ekspresija ZEB1 i LOXL2 gena kod karcinoma rektuma i njihova korelacija sa ekstramuralnom venskom invazijom (EMVI): preliminarna studija",
url = "https://hdl.handle.net/21.15107/rcub_vinar_13104"
}

Kožik, B., Todorović, L., Božović, A., Kolaković, A., Vasiljević, T., Đurić, M., Đermanović, A.,& Mandušić, V.. (2023). Expression of ZEB1 and LOXL2 in rectal carcinoma and their correlation with extramural venous invasion (EMVI): preliminary study. in Anali kancerološke sekcije SLD : 60. Kancerološka nedelja : Knjiga apstrakata
Belgrade : Serbian Medical Society Oncology Section..
https://hdl.handle.net/21.15107/rcub_vinar_13104

Kožik B, Todorović L, Božović A, Kolaković A, Vasiljević T, Đurić M, Đermanović A, Mandušić V. Expression of ZEB1 and LOXL2 in rectal carcinoma and their correlation with extramural venous invasion (EMVI): preliminary study. in Anali kancerološke sekcije SLD : 60. Kancerološka nedelja : Knjiga apstrakata. 2023;.
https://hdl.handle.net/21.15107/rcub_vinar_13104 .

Kožik, Bojana, Todorović, Lidija, Božović, Ana, Kolaković, Ana, Vasiljević, Tijana, Đurić, Mladen, Đermanović, Aleksandar, Mandušić, Vesna, "Expression of ZEB1 and LOXL2 in rectal carcinoma and their correlation with extramural venous invasion (EMVI): preliminary study" in Anali kancerološke sekcije SLD : 60. Kancerološka nedelja : Knjiga apstrakata (2023),
https://hdl.handle.net/21.15107/rcub_vinar_13104 .

TY  - CONF
AU  - Đurić, Mladen
AU  - Kožik, Bojana
AU  - Vasiljević, Tijana
AU  - Đermanović, Aleksandar
AU  - Stanulović, Nevena
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12637
AB  - Background: Rectal carcinoma (RC), a common malignancy of the gastrointesƟ nal tract, remains a great clinical challenge due to the increased risk of local and/or systemic recurrence. The mechanism of primary tumor progression and disseminaƟ on may be the crucial prognosƟ c factor. Direct vascular spread, especially venous invasion, has been previously recognized and validated as an important predictor of adverse prognosis. Extramural venous invasion (EMVI) is characterized by the presence of tumor cells within veins outside the bowel wall and is strongly associated with poor survival, increased risk of local recurrence, systemic recurrence, and death. The aim of this study is to examine the prognosƟ c value of pathologically detected EMVI and its relaƟ onship with other available clinicopathological parameters of paƟ ents with RC. PaƟ ents and Methods: This retrospecƟ ve study included 100 untreated and non-metastaƟ c RC paƟ ents (50 EMVI+ and 50 EMVI-) who underwent curaƟ ve resecƟ on between January 2016 and June 2018 and were followed for the next fi ve years (median follow-up of 71.1 months). The presence of EMVI was assessed on standard hematoxylin and eosin-stained histolological secƟ ons of postoperaƟ ve tumor specimens samples, confi rmed by a consultant pathologist in arbitrary cases, and in accordance with validated College of American Pathologist (CAP) guidelines. Results: The presence of EMVI within a selected cohort of RC paƟ ents signifi cantly associated with female gender (p=0.039), T4 stage (p=<0.001), N2 stage (p=<0.001), less number (n≤3) of involved lymph nodes (p=<0.001), excessive lymphaƟ c infi ltraƟ on (p=0.044), presence of perineural invasion (p=0.002), posiƟ ve circumferenƟ al margin (CRM) (p=0.003), and TNMIII stage (p=<0.001). In addiƟ on, within EMVI+ paƟ ents, metastases, dominantly in the liver (13/19, 68%), and death outcomes were more frequent events (p=0.013 and p=0.032, respecƟ vely), while survival analyses revealed that EMVI+ paƟ ents had signifi cantly shorter overall survival (OS, p=0.035) and disease-free survival (DFS, p=0.030). Conclusion: Obtained results strongly suggest that the EMVI type of vascular invasion, considered independently of classical stage parameters and separately from lymphaƟ c invasion, has the potenƟ al to be a reliable predictor of the course and outcome of the disease, which should be confi rmed on a larger cohort of paƟ ents with RC.
PB  - Belgrade : Serbian Association for Cancer Research
C3  - Oncology Insights
T1  - Prognostic significance of pathologically detected extramural venous invasion (EMVI) in rectal carcinoma
IS  - 1
SP  - 90
EP  - 90
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12637
ER  - 

@conference{
author = "Đurić, Mladen and Kožik, Bojana and Vasiljević, Tijana and Đermanović, Aleksandar and Stanulović, Nevena",
year = "2023",
abstract = "Background: Rectal carcinoma (RC), a common malignancy of the gastrointesƟ nal tract, remains a great clinical challenge due to the increased risk of local and/or systemic recurrence. The mechanism of primary tumor progression and disseminaƟ on may be the crucial prognosƟ c factor. Direct vascular spread, especially venous invasion, has been previously recognized and validated as an important predictor of adverse prognosis. Extramural venous invasion (EMVI) is characterized by the presence of tumor cells within veins outside the bowel wall and is strongly associated with poor survival, increased risk of local recurrence, systemic recurrence, and death. The aim of this study is to examine the prognosƟ c value of pathologically detected EMVI and its relaƟ onship with other available clinicopathological parameters of paƟ ents with RC. PaƟ ents and Methods: This retrospecƟ ve study included 100 untreated and non-metastaƟ c RC paƟ ents (50 EMVI+ and 50 EMVI-) who underwent curaƟ ve resecƟ on between January 2016 and June 2018 and were followed for the next fi ve years (median follow-up of 71.1 months). The presence of EMVI was assessed on standard hematoxylin and eosin-stained histolological secƟ ons of postoperaƟ ve tumor specimens samples, confi rmed by a consultant pathologist in arbitrary cases, and in accordance with validated College of American Pathologist (CAP) guidelines. Results: The presence of EMVI within a selected cohort of RC paƟ ents signifi cantly associated with female gender (p=0.039), T4 stage (p=<0.001), N2 stage (p=<0.001), less number (n≤3) of involved lymph nodes (p=<0.001), excessive lymphaƟ c infi ltraƟ on (p=0.044), presence of perineural invasion (p=0.002), posiƟ ve circumferenƟ al margin (CRM) (p=0.003), and TNMIII stage (p=<0.001). In addiƟ on, within EMVI+ paƟ ents, metastases, dominantly in the liver (13/19, 68%), and death outcomes were more frequent events (p=0.013 and p=0.032, respecƟ vely), while survival analyses revealed that EMVI+ paƟ ents had signifi cantly shorter overall survival (OS, p=0.035) and disease-free survival (DFS, p=0.030). Conclusion: Obtained results strongly suggest that the EMVI type of vascular invasion, considered independently of classical stage parameters and separately from lymphaƟ c invasion, has the potenƟ al to be a reliable predictor of the course and outcome of the disease, which should be confi rmed on a larger cohort of paƟ ents with RC.",
publisher = "Belgrade : Serbian Association for Cancer Research",
journal = "Oncology Insights",
title = "Prognostic significance of pathologically detected extramural venous invasion (EMVI) in rectal carcinoma",
number = "1",
pages = "90-90",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12637"
}

Đurić, M., Kožik, B., Vasiljević, T., Đermanović, A.,& Stanulović, N.. (2023). Prognostic significance of pathologically detected extramural venous invasion (EMVI) in rectal carcinoma. in Oncology Insights
Belgrade : Serbian Association for Cancer Research.(1), 90-90.
https://hdl.handle.net/21.15107/rcub_vinar_12637

Đurić M, Kožik B, Vasiljević T, Đermanović A, Stanulović N. Prognostic significance of pathologically detected extramural venous invasion (EMVI) in rectal carcinoma. in Oncology Insights. 2023;(1):90-90.
https://hdl.handle.net/21.15107/rcub_vinar_12637 .

Đurić, Mladen, Kožik, Bojana, Vasiljević, Tijana, Đermanović, Aleksandar, Stanulović, Nevena, "Prognostic significance of pathologically detected extramural venous invasion (EMVI) in rectal carcinoma" in Oncology Insights, no. 1 (2023):90-90,
https://hdl.handle.net/21.15107/rcub_vinar_12637 .