TY  - JOUR
AU  - Markićević, Milan
AU  - Džodić, Radan R.
AU  - Buta, Marko
AU  - Kanjer, Ksenija
AU  - Mandušić, Vesna
AU  - Nešković-Konstantinović, Zora
AU  - Nikolić-Vukosavljević, Dragica
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/203
AB  - Background. A role of an estrogen-regulated, autocrine motogenic factor was assumed to be a major biological role of trefoil factor 1 (TFF1) in breast cancer. TFF1 is regarded as a predictive factor for positive response to endocrine therapy in breast cancer patients. The aim of our study was to examine TFF1 level distribution in breast carcinomas in order to distinguish estrogen-independent from estrogen-dependent TFF1 expression and to evaluate clinical usefulness of TFF1 status in early breast cancer during the first 3 years of follow-up. Methods. The study included 226 patients with primary operable invasive early breast carcinomas for whom an equal, a 3-year follow-up was conducted. TFF1 levels as well as estrogen receptor (ER) and progesterone receptor (PR) levels were measured in cytosolic extracts of tumor samples by immunoradiometric assay or by use of classical biochemical method, respectively. Non-parametric statistical tests were applied for data analyses. Results. Statistical analysis revealed that TFF1 levels were significantly higher in premenopausal patients (p=0.02), or in tumors with: lower histological grade (p LT 0.001), positive ER or PR status (p LT 0.001, in both cases). On the basis of TFF1 level distribution between ER-negative and ER-positive postmenopausal patients with tumors of different histological grade, 14 ng/mg was set as the cut-off value to distinguish estrogen-independent from estrogen-dependent TFF1 expression in breast cancer. Depending on menopausal and PR status, positive TFF1 status identified patients at opposite risk for relapse among ER-positive patients with grade II tumors. Among ER-and and PR-positive premenopausal patients with grade II tumors, TFF1 status alone identified patients at opposite risk for relapse. Conclusions. Determination of TFF1 status might identify patients at different risk for relapse and help in making decision on administering adjuvant therapy for early breast cancer patients during the first 3 years of follow-up.
T2  - International Journal of Medical Sciences
T1  - Trefoil Factor 1 in Early Breast Carcinoma: A Potential Indicator of Clinical Outcome during the First 3 Years of Follow-Up
VL  - 11
IS  - 7
SP  - 663
EP  - 673
DO  - 10.7150/ijms.8194
ER  - 

@article{
author = "Markićević, Milan and Džodić, Radan R. and Buta, Marko and Kanjer, Ksenija and Mandušić, Vesna and Nešković-Konstantinović, Zora and Nikolić-Vukosavljević, Dragica",
year = "2014",
abstract = "Background. A role of an estrogen-regulated, autocrine motogenic factor was assumed to be a major biological role of trefoil factor 1 (TFF1) in breast cancer. TFF1 is regarded as a predictive factor for positive response to endocrine therapy in breast cancer patients. The aim of our study was to examine TFF1 level distribution in breast carcinomas in order to distinguish estrogen-independent from estrogen-dependent TFF1 expression and to evaluate clinical usefulness of TFF1 status in early breast cancer during the first 3 years of follow-up. Methods. The study included 226 patients with primary operable invasive early breast carcinomas for whom an equal, a 3-year follow-up was conducted. TFF1 levels as well as estrogen receptor (ER) and progesterone receptor (PR) levels were measured in cytosolic extracts of tumor samples by immunoradiometric assay or by use of classical biochemical method, respectively. Non-parametric statistical tests were applied for data analyses. Results. Statistical analysis revealed that TFF1 levels were significantly higher in premenopausal patients (p=0.02), or in tumors with: lower histological grade (p LT 0.001), positive ER or PR status (p LT 0.001, in both cases). On the basis of TFF1 level distribution between ER-negative and ER-positive postmenopausal patients with tumors of different histological grade, 14 ng/mg was set as the cut-off value to distinguish estrogen-independent from estrogen-dependent TFF1 expression in breast cancer. Depending on menopausal and PR status, positive TFF1 status identified patients at opposite risk for relapse among ER-positive patients with grade II tumors. Among ER-and and PR-positive premenopausal patients with grade II tumors, TFF1 status alone identified patients at opposite risk for relapse. Conclusions. Determination of TFF1 status might identify patients at different risk for relapse and help in making decision on administering adjuvant therapy for early breast cancer patients during the first 3 years of follow-up.",
journal = "International Journal of Medical Sciences",
title = "Trefoil Factor 1 in Early Breast Carcinoma: A Potential Indicator of Clinical Outcome during the First 3 Years of Follow-Up",
volume = "11",
number = "7",
pages = "663-673",
doi = "10.7150/ijms.8194"
}

Markićević, M., Džodić, R. R., Buta, M., Kanjer, K., Mandušić, V., Nešković-Konstantinović, Z.,& Nikolić-Vukosavljević, D.. (2014). Trefoil Factor 1 in Early Breast Carcinoma: A Potential Indicator of Clinical Outcome during the First 3 Years of Follow-Up. in International Journal of Medical Sciences, 11(7), 663-673.
https://doi.org/10.7150/ijms.8194

Markićević M, Džodić RR, Buta M, Kanjer K, Mandušić V, Nešković-Konstantinović Z, Nikolić-Vukosavljević D. Trefoil Factor 1 in Early Breast Carcinoma: A Potential Indicator of Clinical Outcome during the First 3 Years of Follow-Up. in International Journal of Medical Sciences. 2014;11(7):663-673.
doi:10.7150/ijms.8194 .

Markićević, Milan, Džodić, Radan R., Buta, Marko, Kanjer, Ksenija, Mandušić, Vesna, Nešković-Konstantinović, Zora, Nikolić-Vukosavljević, Dragica, "Trefoil Factor 1 in Early Breast Carcinoma: A Potential Indicator of Clinical Outcome during the First 3 Years of Follow-Up" in International Journal of Medical Sciences, 11, no. 7 (2014):663-673,
https://doi.org/10.7150/ijms.8194 . .

TY  - JOUR
AU  - Božović, Ana M.
AU  - Markićević, Milan
AU  - Dimitrijević, Bogomir B.
AU  - Jovanović-Ćupić, Snežana P.
AU  - Krajnović, Milena M.
AU  - Lukić, Silvana
AU  - Mandušić, Vesna
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5647
AB  - The aim of the study was to assess how hypermethylation of the ON promoter of the estrogen receptor beta (ER beta) gene affects its expression (at the mRNA and protein level) and to correlate these with some clinical and histopathological parameters. A total of 131 samples of frozen breast cancer tissue was analyzed. A custom-designed, two-step PCR method was used to measure the methylation index of the ER beta gene ON promoter region. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed to quantify mRNA of the ER beta 1 isoform, while ER beta 1 protein was determined using the Western blot method. There was a significant difference in the methylation index of the ER beta gene ON promoter between the groups of patients with negative and positive axillary lymph node status (P = 0.03). In addition, the methylation index of the ON promoter was positively correlated with estrogen receptor alfa (ER alpha) protein levels (q = 0.31, P = 0.02). There was a significant difference in the methylation index of the ON promoter between the progesterone receptor (PR)-negative and PR-positive groups of patients (P = 0.01). ER beta 1 protein levels were negatively correlated with ER alpha protein (q = -0.27, P LT 0.01). The methylation index of the ON promoter could be a more reliable additional parameter for prediction and/or prognosis in breast cancer than ER beta 1-mRNA and/or protein levels.
T2  - Medical Oncology
T1  - Potential clinical significance of ER beta ON promoter methylation in sporadic breast cancer
VL  - 30
IS  - 3
DO  - 10.1007/s12032-013-0642-4
ER  - 

@article{
author = "Božović, Ana M. and Markićević, Milan and Dimitrijević, Bogomir B. and Jovanović-Ćupić, Snežana P. and Krajnović, Milena M. and Lukić, Silvana and Mandušić, Vesna",
year = "2013",
abstract = "The aim of the study was to assess how hypermethylation of the ON promoter of the estrogen receptor beta (ER beta) gene affects its expression (at the mRNA and protein level) and to correlate these with some clinical and histopathological parameters. A total of 131 samples of frozen breast cancer tissue was analyzed. A custom-designed, two-step PCR method was used to measure the methylation index of the ER beta gene ON promoter region. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed to quantify mRNA of the ER beta 1 isoform, while ER beta 1 protein was determined using the Western blot method. There was a significant difference in the methylation index of the ER beta gene ON promoter between the groups of patients with negative and positive axillary lymph node status (P = 0.03). In addition, the methylation index of the ON promoter was positively correlated with estrogen receptor alfa (ER alpha) protein levels (q = 0.31, P = 0.02). There was a significant difference in the methylation index of the ON promoter between the progesterone receptor (PR)-negative and PR-positive groups of patients (P = 0.01). ER beta 1 protein levels were negatively correlated with ER alpha protein (q = -0.27, P LT 0.01). The methylation index of the ON promoter could be a more reliable additional parameter for prediction and/or prognosis in breast cancer than ER beta 1-mRNA and/or protein levels.",
journal = "Medical Oncology",
title = "Potential clinical significance of ER beta ON promoter methylation in sporadic breast cancer",
volume = "30",
number = "3",
doi = "10.1007/s12032-013-0642-4"
}

Božović, A. M., Markićević, M., Dimitrijević, B. B., Jovanović-Ćupić, S. P., Krajnović, M. M., Lukić, S.,& Mandušić, V.. (2013). Potential clinical significance of ER beta ON promoter methylation in sporadic breast cancer. in Medical Oncology, 30(3).
https://doi.org/10.1007/s12032-013-0642-4

Božović AM, Markićević M, Dimitrijević BB, Jovanović-Ćupić SP, Krajnović MM, Lukić S, Mandušić V. Potential clinical significance of ER beta ON promoter methylation in sporadic breast cancer. in Medical Oncology. 2013;30(3).
doi:10.1007/s12032-013-0642-4 .

Božović, Ana M., Markićević, Milan, Dimitrijević, Bogomir B., Jovanović-Ćupić, Snežana P., Krajnović, Milena M., Lukić, Silvana, Mandušić, Vesna, "Potential clinical significance of ER beta ON promoter methylation in sporadic breast cancer" in Medical Oncology, 30, no. 3 (2013),
https://doi.org/10.1007/s12032-013-0642-4 . .

TY  - JOUR
AU  - Markićević, Milan
AU  - Kanjer, Ksenija
AU  - Mandušić, Vesna
AU  - Buta, Marko
AU  - Nešković-Konstantinović, Zora
AU  - Nikolić-Vukosavljević, Dragica
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5683
AB  - Aim: The aim of this study was to evaluate clinical usefulness of cathepsin D status in early breast cancer during the first 3 years of follow-up. Patients and methods: The study included 226 patients with histologically verified, primary operable invasive early breast carcinomas. Concentrations of estrogen receptor (ER) and progesterone receptor (PR) in breast tumor cytosols were measured by use of the classical biochemical method. The concentration of three cathepsin D forms (52-, 48- and 34-kDa proteins) was determined by a radioimmunoassay Results: On the basis of differences in cathepsin D levels either within an ER-/PR- phenotype or between this and either ER+/PR+ or ER+/PR- phenotypes, a concentration of 39 pmol/mg was determined as the cutoff value for distinguishing estrogen-regulated cathepsin D expression. Estrogen-regulated cathepsin D expression was recognized as a high-risk biomarker for low-risk (histological grade I) breast cancer patients and as a low-risk biomarker for high-risk patients (pN(+) pT2,3). Conclusion: Determination of cathepsin D status in breast cancer might identify patients at different risk for relapse and might facilitate the selection of more or less aggressive adjuvant therapy for early breast cancer patients during the first 3 years of follow-up.
T2  - Biomarkers in Medicine
T1  - Cathepsin D as an indicator of clinical outcome in early breast carcinoma during the first 3 years of follow-up
VL  - 7
IS  - 5
SP  - 747
EP  - 758
DO  - 10.2217/bmm.13.62
ER  - 

@article{
author = "Markićević, Milan and Kanjer, Ksenija and Mandušić, Vesna and Buta, Marko and Nešković-Konstantinović, Zora and Nikolić-Vukosavljević, Dragica",
year = "2013",
abstract = "Aim: The aim of this study was to evaluate clinical usefulness of cathepsin D status in early breast cancer during the first 3 years of follow-up. Patients and methods: The study included 226 patients with histologically verified, primary operable invasive early breast carcinomas. Concentrations of estrogen receptor (ER) and progesterone receptor (PR) in breast tumor cytosols were measured by use of the classical biochemical method. The concentration of three cathepsin D forms (52-, 48- and 34-kDa proteins) was determined by a radioimmunoassay Results: On the basis of differences in cathepsin D levels either within an ER-/PR- phenotype or between this and either ER+/PR+ or ER+/PR- phenotypes, a concentration of 39 pmol/mg was determined as the cutoff value for distinguishing estrogen-regulated cathepsin D expression. Estrogen-regulated cathepsin D expression was recognized as a high-risk biomarker for low-risk (histological grade I) breast cancer patients and as a low-risk biomarker for high-risk patients (pN(+) pT2,3). Conclusion: Determination of cathepsin D status in breast cancer might identify patients at different risk for relapse and might facilitate the selection of more or less aggressive adjuvant therapy for early breast cancer patients during the first 3 years of follow-up.",
journal = "Biomarkers in Medicine",
title = "Cathepsin D as an indicator of clinical outcome in early breast carcinoma during the first 3 years of follow-up",
volume = "7",
number = "5",
pages = "747-758",
doi = "10.2217/bmm.13.62"
}

Markićević, M., Kanjer, K., Mandušić, V., Buta, M., Nešković-Konstantinović, Z.,& Nikolić-Vukosavljević, D.. (2013). Cathepsin D as an indicator of clinical outcome in early breast carcinoma during the first 3 years of follow-up. in Biomarkers in Medicine, 7(5), 747-758.
https://doi.org/10.2217/bmm.13.62

Markićević M, Kanjer K, Mandušić V, Buta M, Nešković-Konstantinović Z, Nikolić-Vukosavljević D. Cathepsin D as an indicator of clinical outcome in early breast carcinoma during the first 3 years of follow-up. in Biomarkers in Medicine. 2013;7(5):747-758.
doi:10.2217/bmm.13.62 .

Markićević, Milan, Kanjer, Ksenija, Mandušić, Vesna, Buta, Marko, Nešković-Konstantinović, Zora, Nikolić-Vukosavljević, Dragica, "Cathepsin D as an indicator of clinical outcome in early breast carcinoma during the first 3 years of follow-up" in Biomarkers in Medicine, 7, no. 5 (2013):747-758,
https://doi.org/10.2217/bmm.13.62 . .

TY  - JOUR
AU  - Mandušić, Vesna
AU  - Dimitrijević, Bogomir B.
AU  - Nikolić-Vukosavljević, Dragica
AU  - Nešković-Konstantinović, Zora
AU  - Kanjer, Ksenija
AU  - Hamann, Ute
PY  - 2012
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5002
AB  - Background: In breast cancer, little is known about the consequences of co-expression of ER alpha with the second estrogen receptor, ER beta, and its isoforms in light of their joint prognostic value. Previously reported correlations have been based mostly on independent ER alpha and ER beta expression levels in breast tumors. Purpose: To address whether the expression ratio of ER alpha and ER beta and its isoforms may be a more important parameter than their absolute levels, we analyzed relative mRNA expression ratios of ER beta 1 to ER beta 2 and ER alpha in 74 clinical samples of invasive breast cancer including 39 early-onset and 35 late-onset breast cancers. Expression levels were correlated with clinical and histopathological parameters and disease-free interval. Results: A specific correlation of ER beta 1 expression levels with tumor size was detected in early-onset breast cancer patients and of ER beta 2 levels with tumor size in late-onset patients. Expression of both ER beta isoforms inversely correlated with expression of the two estrogen regulated genes, progesterone receptor and pS2 in both groups. Higher levels of ER beta 2 than ER beta 1 isoform were associated with a better outcome in late-onset patients. Conclusions: Our results suggest that different isoforms of ER beta may be involved in suppression of tumor growth in young and elder patients and may have different prognostic values. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
T2  - Cancer Letters
T1  - Different associations of estrogen receptor beta isoforms, ER beta 1 and ER beta 2, expression levels with tumor size and survival in early- and late-onset breast cancer
VL  - 321
IS  - 1
SP  - 73
EP  - 79
DO  - 10.1016/j.canlet.2012.02.022
ER  - 

@article{
author = "Mandušić, Vesna and Dimitrijević, Bogomir B. and Nikolić-Vukosavljević, Dragica and Nešković-Konstantinović, Zora and Kanjer, Ksenija and Hamann, Ute",
year = "2012",
abstract = "Background: In breast cancer, little is known about the consequences of co-expression of ER alpha with the second estrogen receptor, ER beta, and its isoforms in light of their joint prognostic value. Previously reported correlations have been based mostly on independent ER alpha and ER beta expression levels in breast tumors. Purpose: To address whether the expression ratio of ER alpha and ER beta and its isoforms may be a more important parameter than their absolute levels, we analyzed relative mRNA expression ratios of ER beta 1 to ER beta 2 and ER alpha in 74 clinical samples of invasive breast cancer including 39 early-onset and 35 late-onset breast cancers. Expression levels were correlated with clinical and histopathological parameters and disease-free interval. Results: A specific correlation of ER beta 1 expression levels with tumor size was detected in early-onset breast cancer patients and of ER beta 2 levels with tumor size in late-onset patients. Expression of both ER beta isoforms inversely correlated with expression of the two estrogen regulated genes, progesterone receptor and pS2 in both groups. Higher levels of ER beta 2 than ER beta 1 isoform were associated with a better outcome in late-onset patients. Conclusions: Our results suggest that different isoforms of ER beta may be involved in suppression of tumor growth in young and elder patients and may have different prognostic values. (C) 2012 Elsevier Ireland Ltd. All rights reserved.",
journal = "Cancer Letters",
title = "Different associations of estrogen receptor beta isoforms, ER beta 1 and ER beta 2, expression levels with tumor size and survival in early- and late-onset breast cancer",
volume = "321",
number = "1",
pages = "73-79",
doi = "10.1016/j.canlet.2012.02.022"
}

Mandušić, V., Dimitrijević, B. B., Nikolić-Vukosavljević, D., Nešković-Konstantinović, Z., Kanjer, K.,& Hamann, U.. (2012). Different associations of estrogen receptor beta isoforms, ER beta 1 and ER beta 2, expression levels with tumor size and survival in early- and late-onset breast cancer. in Cancer Letters, 321(1), 73-79.
https://doi.org/10.1016/j.canlet.2012.02.022

Mandušić V, Dimitrijević BB, Nikolić-Vukosavljević D, Nešković-Konstantinović Z, Kanjer K, Hamann U. Different associations of estrogen receptor beta isoforms, ER beta 1 and ER beta 2, expression levels with tumor size and survival in early- and late-onset breast cancer. in Cancer Letters. 2012;321(1):73-79.
doi:10.1016/j.canlet.2012.02.022 .

Mandušić, Vesna, Dimitrijević, Bogomir B., Nikolić-Vukosavljević, Dragica, Nešković-Konstantinović, Zora, Kanjer, Ksenija, Hamann, Ute, "Different associations of estrogen receptor beta isoforms, ER beta 1 and ER beta 2, expression levels with tumor size and survival in early- and late-onset breast cancer" in Cancer Letters, 321, no. 1 (2012):73-79,
https://doi.org/10.1016/j.canlet.2012.02.022 . .