TY  - JOUR
AU  - Stanojević, Boban
AU  - Saenko, Vladimir
AU  - Todorović, Lidija
AU  - Petrović, Nina
AU  - Nikolić, Dragan
AU  - Živaljević, Vladan R.
AU  - Paunović, Ivan R.
AU  - Nakashima, Masahiro
AU  - Yamashita, Shunichi
AU  - Džodić, Radan R.
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/340
AB  - Alterations of the von Hippel-Lindau (VHL) tumor suppressor gene can cause different hereditary tumors associated with VHL syndrome, but the potential role of the VHL gene in papillary thyroid carcinoma (PTC) has not been characterized. This study set out to investigate the relationship of VHL expression level with clinicopathological features of PTC in an ethnically and geographically homogenous group of 264 patients from Serbia, for the first time. Multivariate logistic regression analysis showed a strong correlation between low level of VHL expression and advanced clinical stage (OR=5.78, 95% CI 3.17-10.53, P LT 0.0001), classical papillary morphology of the tumor (OR=2.92, 95% CI 1.33-6.44, P=0.008) and multifocality (OR=1.96, 95% CI 1.06-3.62, P=0.031). In disease-free survival analysis, low VHL expression had marginal significance (P=0.0502 by the log-rank test) but did not appear to be an independent predictor of the risk for chance of faster recurrence in a proportion hazards model. No somatic mutations or evidence of VHL downregulation via promoter hypermethylation in PTC were found. The results indicate that the decrease of VHL expression associates with tumor progression but the mechanism of downregulation remains to be elucidated.
T2  - PLOS One
T1  - Low VHL mRNA Expression is Associated with More Aggressive Tumor Features of Papillary Thyroid Carcinoma
VL  - 9
IS  - 12
DO  - 10.1371/journal.pone.0114511
ER  - 

@article{
author = "Stanojević, Boban and Saenko, Vladimir and Todorović, Lidija and Petrović, Nina and Nikolić, Dragan and Živaljević, Vladan R. and Paunović, Ivan R. and Nakashima, Masahiro and Yamashita, Shunichi and Džodić, Radan R.",
year = "2014",
abstract = "Alterations of the von Hippel-Lindau (VHL) tumor suppressor gene can cause different hereditary tumors associated with VHL syndrome, but the potential role of the VHL gene in papillary thyroid carcinoma (PTC) has not been characterized. This study set out to investigate the relationship of VHL expression level with clinicopathological features of PTC in an ethnically and geographically homogenous group of 264 patients from Serbia, for the first time. Multivariate logistic regression analysis showed a strong correlation between low level of VHL expression and advanced clinical stage (OR=5.78, 95% CI 3.17-10.53, P LT 0.0001), classical papillary morphology of the tumor (OR=2.92, 95% CI 1.33-6.44, P=0.008) and multifocality (OR=1.96, 95% CI 1.06-3.62, P=0.031). In disease-free survival analysis, low VHL expression had marginal significance (P=0.0502 by the log-rank test) but did not appear to be an independent predictor of the risk for chance of faster recurrence in a proportion hazards model. No somatic mutations or evidence of VHL downregulation via promoter hypermethylation in PTC were found. The results indicate that the decrease of VHL expression associates with tumor progression but the mechanism of downregulation remains to be elucidated.",
journal = "PLOS One",
title = "Low VHL mRNA Expression is Associated with More Aggressive Tumor Features of Papillary Thyroid Carcinoma",
volume = "9",
number = "12",
doi = "10.1371/journal.pone.0114511"
}

Stanojević, B., Saenko, V., Todorović, L., Petrović, N., Nikolić, D., Živaljević, V. R., Paunović, I. R., Nakashima, M., Yamashita, S.,& Džodić, R. R.. (2014). Low VHL mRNA Expression is Associated with More Aggressive Tumor Features of Papillary Thyroid Carcinoma. in PLOS One, 9(12).
https://doi.org/10.1371/journal.pone.0114511

Stanojević B, Saenko V, Todorović L, Petrović N, Nikolić D, Živaljević VR, Paunović IR, Nakashima M, Yamashita S, Džodić RR. Low VHL mRNA Expression is Associated with More Aggressive Tumor Features of Papillary Thyroid Carcinoma. in PLOS One. 2014;9(12).
doi:10.1371/journal.pone.0114511 .

Stanojević, Boban, Saenko, Vladimir, Todorović, Lidija, Petrović, Nina, Nikolić, Dragan, Živaljević, Vladan R., Paunović, Ivan R., Nakashima, Masahiro, Yamashita, Shunichi, Džodić, Radan R., "Low VHL mRNA Expression is Associated with More Aggressive Tumor Features of Papillary Thyroid Carcinoma" in PLOS One, 9, no. 12 (2014),
https://doi.org/10.1371/journal.pone.0114511 . .

TY  - JOUR
AU  - Mussazhanova, Zhanna
AU  - Miura, Shiro
AU  - Stanojević, Boban
AU  - Rougounovitch, Tatiana
AU  - Saenko, Vladimir
AU  - Shiraishi, Toshio
AU  - Kurashige, Tomomi
AU  - Shichijo, Kazuko
AU  - Kaneko, Kenichi
AU  - Takahashi, Haruo
AU  - Ito, Masahiro
AU  - Nakashima, Masahiro
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5911
AB  - Background: Neuroendocrine tumor (NET) of the thyroid other than medullary carcinoma is extremely rare. We describe here a case of calcitonin-negative small cell neuroendocrine carcinoma (SCNEC), which occurred in a thyroid gland that had previously been irradiated at high dose (60Gy) for pharyngeal cancer, with molecular analyses for follicular cell origin. Patient Findings: The tumor cells were small with fine chromatin, inconspicuous nucleoli, and inapparent cytoplasm, and showed neuroendocrine architectures such as palisading, rosettes, and trabeculae. Mitotic figures were numerous exceeding 10 mitoses per 10 high-power fields. The tumor cells invaded into several vessels and metastasized to regional lymph nodes. Immunohistochemically, the tumor cells were strongly positive for neuroendocrine markers and thyroglobulin (Tg), a marker of thyroid follicular cells but negative for calcitonin and carcinoembryonic antigen (CEA). Expression of Tg and thyrotropin receptor (TSHR) were confirmed by quantitative real-time polymerase chain reaction (RT-PCR). Ki-67 labeling index was more than 70% in the tumor cells. Taken together, the tumor was diagnosed as SCNEC of the thyroid. Genetic analyses also revealed microsatellite abnormalities of the phosphatase and tensin homolog (PTEN) gene, suggesting that functional loss of PTEN contributes to carcinogenesis. Conclusions: This is the first report describing a SCNEC of the thyroid with molecular analyses that provide evidence for a follicular epithelial origin.
T2  - Thyroid
T1  - Radiation-Associated Small Cell Neuroendocrine Carcinoma of the Thyroid: A Case Report with Molecular Analyses
VL  - 24
IS  - 3
SP  - 593
EP  - 598
DO  - 10.1089/thy.2013.0214
ER  - 

@article{
author = "Mussazhanova, Zhanna and Miura, Shiro and Stanojević, Boban and Rougounovitch, Tatiana and Saenko, Vladimir and Shiraishi, Toshio and Kurashige, Tomomi and Shichijo, Kazuko and Kaneko, Kenichi and Takahashi, Haruo and Ito, Masahiro and Nakashima, Masahiro",
year = "2014",
abstract = "Background: Neuroendocrine tumor (NET) of the thyroid other than medullary carcinoma is extremely rare. We describe here a case of calcitonin-negative small cell neuroendocrine carcinoma (SCNEC), which occurred in a thyroid gland that had previously been irradiated at high dose (60Gy) for pharyngeal cancer, with molecular analyses for follicular cell origin. Patient Findings: The tumor cells were small with fine chromatin, inconspicuous nucleoli, and inapparent cytoplasm, and showed neuroendocrine architectures such as palisading, rosettes, and trabeculae. Mitotic figures were numerous exceeding 10 mitoses per 10 high-power fields. The tumor cells invaded into several vessels and metastasized to regional lymph nodes. Immunohistochemically, the tumor cells were strongly positive for neuroendocrine markers and thyroglobulin (Tg), a marker of thyroid follicular cells but negative for calcitonin and carcinoembryonic antigen (CEA). Expression of Tg and thyrotropin receptor (TSHR) were confirmed by quantitative real-time polymerase chain reaction (RT-PCR). Ki-67 labeling index was more than 70% in the tumor cells. Taken together, the tumor was diagnosed as SCNEC of the thyroid. Genetic analyses also revealed microsatellite abnormalities of the phosphatase and tensin homolog (PTEN) gene, suggesting that functional loss of PTEN contributes to carcinogenesis. Conclusions: This is the first report describing a SCNEC of the thyroid with molecular analyses that provide evidence for a follicular epithelial origin.",
journal = "Thyroid",
title = "Radiation-Associated Small Cell Neuroendocrine Carcinoma of the Thyroid: A Case Report with Molecular Analyses",
volume = "24",
number = "3",
pages = "593-598",
doi = "10.1089/thy.2013.0214"
}

Mussazhanova, Z., Miura, S., Stanojević, B., Rougounovitch, T., Saenko, V., Shiraishi, T., Kurashige, T., Shichijo, K., Kaneko, K., Takahashi, H., Ito, M.,& Nakashima, M.. (2014). Radiation-Associated Small Cell Neuroendocrine Carcinoma of the Thyroid: A Case Report with Molecular Analyses. in Thyroid, 24(3), 593-598.
https://doi.org/10.1089/thy.2013.0214

Mussazhanova Z, Miura S, Stanojević B, Rougounovitch T, Saenko V, Shiraishi T, Kurashige T, Shichijo K, Kaneko K, Takahashi H, Ito M, Nakashima M. Radiation-Associated Small Cell Neuroendocrine Carcinoma of the Thyroid: A Case Report with Molecular Analyses. in Thyroid. 2014;24(3):593-598.
doi:10.1089/thy.2013.0214 .

Mussazhanova, Zhanna, Miura, Shiro, Stanojević, Boban, Rougounovitch, Tatiana, Saenko, Vladimir, Shiraishi, Toshio, Kurashige, Tomomi, Shichijo, Kazuko, Kaneko, Kenichi, Takahashi, Haruo, Ito, Masahiro, Nakashima, Masahiro, "Radiation-Associated Small Cell Neuroendocrine Carcinoma of the Thyroid: A Case Report with Molecular Analyses" in Thyroid, 24, no. 3 (2014):593-598,
https://doi.org/10.1089/thy.2013.0214 . .

TY  - JOUR
AU  - Mussazhanova, Zhanna
AU  - Matsuda, Katsuya
AU  - Naruke, Yuki
AU  - Mitsutake, Norisato
AU  - Stanojević, Boban
AU  - Rougounovitch, Tatiana
AU  - Saenko, Vladimir
AU  - Suzuki, Keiji
AU  - Nishihara, Eijyun
AU  - Hirokawa, Mitsuyoshi
AU  - Ito, Masahiro
AU  - Nakashima, Masahiro
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5717
AB  - AimsIn a previous report, we proposed that analysis of 53BP1 expression by immunofluorescence could be a useful tool in estimating the level of genomic instability (GIN), as well as the malignant potential, of thyroid tumours. In an attempt to clarify the value of 53BP1 expression as a new molecular marker for the aggressiveness of thyroid papillary microcarcinoma (PMC), we assessed the association between the type of 53BP1 expression and clinicopathological features such as tumour size, extrathyroidal invasion, lymph node metastasis and BRAF(V600E) mutation of PMC. Methods and resultsA total of 36 surgically resected thyroid tumours, including 13 PMC and 23 conventional papillary thyroid carcinomas (PTC), were available for this study. Analysis using immunofluorescence revealed that the incidence of an abnormal or high DNA damage response (DDR) type of 53BP1 expression was significantly higher in PTC than PMC. BRAF(V600E) mutation was not associated significantly with tumour aggressiveness in either PMC or PTC cases. Abnormal/high DDR type of 53BP1 expression was associated closely with both BRAF(V600E) mutation and papillary and/or trabecular architecture of PMC. ConclusionsAbnormal/high DDR type of 53BP1 expression might be associated with GIN and papillary/trabecular morphology at an early stage of PTC carcinogenesis through BRAF(V600E) mutation.
T2  - Histopathology
T1  - Significance of p53-binding protein 1 (53BP1) expression in thyroid papillary microcarcinoma: association with BRAF(V600E) mutation status
VL  - 63
IS  - 5
SP  - 726
EP  - 734
DO  - 10.1111/his.12233
ER  - 

@article{
author = "Mussazhanova, Zhanna and Matsuda, Katsuya and Naruke, Yuki and Mitsutake, Norisato and Stanojević, Boban and Rougounovitch, Tatiana and Saenko, Vladimir and Suzuki, Keiji and Nishihara, Eijyun and Hirokawa, Mitsuyoshi and Ito, Masahiro and Nakashima, Masahiro",
year = "2013",
abstract = "AimsIn a previous report, we proposed that analysis of 53BP1 expression by immunofluorescence could be a useful tool in estimating the level of genomic instability (GIN), as well as the malignant potential, of thyroid tumours. In an attempt to clarify the value of 53BP1 expression as a new molecular marker for the aggressiveness of thyroid papillary microcarcinoma (PMC), we assessed the association between the type of 53BP1 expression and clinicopathological features such as tumour size, extrathyroidal invasion, lymph node metastasis and BRAF(V600E) mutation of PMC. Methods and resultsA total of 36 surgically resected thyroid tumours, including 13 PMC and 23 conventional papillary thyroid carcinomas (PTC), were available for this study. Analysis using immunofluorescence revealed that the incidence of an abnormal or high DNA damage response (DDR) type of 53BP1 expression was significantly higher in PTC than PMC. BRAF(V600E) mutation was not associated significantly with tumour aggressiveness in either PMC or PTC cases. Abnormal/high DDR type of 53BP1 expression was associated closely with both BRAF(V600E) mutation and papillary and/or trabecular architecture of PMC. ConclusionsAbnormal/high DDR type of 53BP1 expression might be associated with GIN and papillary/trabecular morphology at an early stage of PTC carcinogenesis through BRAF(V600E) mutation.",
journal = "Histopathology",
title = "Significance of p53-binding protein 1 (53BP1) expression in thyroid papillary microcarcinoma: association with BRAF(V600E) mutation status",
volume = "63",
number = "5",
pages = "726-734",
doi = "10.1111/his.12233"
}

Mussazhanova, Z., Matsuda, K., Naruke, Y., Mitsutake, N., Stanojević, B., Rougounovitch, T., Saenko, V., Suzuki, K., Nishihara, E., Hirokawa, M., Ito, M.,& Nakashima, M.. (2013). Significance of p53-binding protein 1 (53BP1) expression in thyroid papillary microcarcinoma: association with BRAF(V600E) mutation status. in Histopathology, 63(5), 726-734.
https://doi.org/10.1111/his.12233

Mussazhanova Z, Matsuda K, Naruke Y, Mitsutake N, Stanojević B, Rougounovitch T, Saenko V, Suzuki K, Nishihara E, Hirokawa M, Ito M, Nakashima M. Significance of p53-binding protein 1 (53BP1) expression in thyroid papillary microcarcinoma: association with BRAF(V600E) mutation status. in Histopathology. 2013;63(5):726-734.
doi:10.1111/his.12233 .

Mussazhanova, Zhanna, Matsuda, Katsuya, Naruke, Yuki, Mitsutake, Norisato, Stanojević, Boban, Rougounovitch, Tatiana, Saenko, Vladimir, Suzuki, Keiji, Nishihara, Eijyun, Hirokawa, Mitsuyoshi, Ito, Masahiro, Nakashima, Masahiro, "Significance of p53-binding protein 1 (53BP1) expression in thyroid papillary microcarcinoma: association with BRAF(V600E) mutation status" in Histopathology, 63, no. 5 (2013):726-734,
https://doi.org/10.1111/his.12233 . .

TY  - JOUR
AU  - Stanojević, Boban
AU  - Džodić, Radan R.
AU  - Saenko, Vladimir
AU  - Milovanović, Zorka M.
AU  - Pupić, Gordana
AU  - Živković, Ognjen
AU  - Marković, Ivan
AU  - Đurišić, Igor
AU  - Buta, Marko
AU  - Dimitrijević, Bogomir B.
AU  - Rogounovitch, Tatiana
AU  - Mitsutake, Norisato
AU  - Mine, Mariko
AU  - Shibata, Yoshisada
AU  - Nakashima, Masahiro
AU  - Yamashita, Shunichi
PY  - 2011
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4401
AB  - Molecular pathogenesis of papillary thyroid carcinoma (PTC) is largely associated with mutational changes in the BRAF, RAS family and RET genes. Our aim was to assess clinico-pathological and prognostic correlations of these PTC-specific gene alterations, with a particular emphasis on the BRAF mutation, in a group of 266 Serbian PTC patients, for the first time. The reference center-based retrospective cohort included 201 (75.6%) females and 65 (24.4%) males aged 48.0 +/- 16.1 years (8-83 years old, range) diagnosed and treated for PTC during 1993-2008. Follow-up period was 53.1 +/- 41.6 months (7-187 months, range). BRAF and RAS mutations were determined by direct sequencing of genomic DNA. RET/PTC rearrangements were analyzed by RT-PCR/Southern blotting. Genetic alterations were detected in 150/266 tumors (56.4%). One tumor displayed two genetic alterations. The BRAF(V600E) was found in 84/266 (31.6%) cases, RAS mutations in 11/266(4.1%) and RET/PTC in 55/266(20.7%; 42/266 (15.8%)RET/PTC1 and 13/266 (4.9%)RET/PTC3). On multivariate analysis BRAF(V600E) was associated with the classical papillary morphology (P = 0.05), the higher pT category (P = 0.05) and advanced clinical stage (P = 0.03). In a proportional hazard model, BRAF(V600E) did not appear to be an independent risk factor for the faster recurrence (P = 0.784). We conclude that under the extensive thyroid surgery and limited application of radioiodine ablation BRAF(V600E) may not be an indicator of poorer disease-free survival during the short to middle follow-up period. However, it has a potential to contribute to patients stratification into high- and low-risk groups.
T2  - Endocrine Journal
T1  - Mutational and clinico-pathological analysis of papillary thyroid carcinoma in Serbia
VL  - 58
IS  - 5
SP  - 381
EP  - 393
DO  - 10.1507/endocrj.K11E-054
ER  - 

@article{
author = "Stanojević, Boban and Džodić, Radan R. and Saenko, Vladimir and Milovanović, Zorka M. and Pupić, Gordana and Živković, Ognjen and Marković, Ivan and Đurišić, Igor and Buta, Marko and Dimitrijević, Bogomir B. and Rogounovitch, Tatiana and Mitsutake, Norisato and Mine, Mariko and Shibata, Yoshisada and Nakashima, Masahiro and Yamashita, Shunichi",
year = "2011",
abstract = "Molecular pathogenesis of papillary thyroid carcinoma (PTC) is largely associated with mutational changes in the BRAF, RAS family and RET genes. Our aim was to assess clinico-pathological and prognostic correlations of these PTC-specific gene alterations, with a particular emphasis on the BRAF mutation, in a group of 266 Serbian PTC patients, for the first time. The reference center-based retrospective cohort included 201 (75.6%) females and 65 (24.4%) males aged 48.0 +/- 16.1 years (8-83 years old, range) diagnosed and treated for PTC during 1993-2008. Follow-up period was 53.1 +/- 41.6 months (7-187 months, range). BRAF and RAS mutations were determined by direct sequencing of genomic DNA. RET/PTC rearrangements were analyzed by RT-PCR/Southern blotting. Genetic alterations were detected in 150/266 tumors (56.4%). One tumor displayed two genetic alterations. The BRAF(V600E) was found in 84/266 (31.6%) cases, RAS mutations in 11/266(4.1%) and RET/PTC in 55/266(20.7%; 42/266 (15.8%)RET/PTC1 and 13/266 (4.9%)RET/PTC3). On multivariate analysis BRAF(V600E) was associated with the classical papillary morphology (P = 0.05), the higher pT category (P = 0.05) and advanced clinical stage (P = 0.03). In a proportional hazard model, BRAF(V600E) did not appear to be an independent risk factor for the faster recurrence (P = 0.784). We conclude that under the extensive thyroid surgery and limited application of radioiodine ablation BRAF(V600E) may not be an indicator of poorer disease-free survival during the short to middle follow-up period. However, it has a potential to contribute to patients stratification into high- and low-risk groups.",
journal = "Endocrine Journal",
title = "Mutational and clinico-pathological analysis of papillary thyroid carcinoma in Serbia",
volume = "58",
number = "5",
pages = "381-393",
doi = "10.1507/endocrj.K11E-054"
}

Stanojević, B., Džodić, R. R., Saenko, V., Milovanović, Z. M., Pupić, G., Živković, O., Marković, I., Đurišić, I., Buta, M., Dimitrijević, B. B., Rogounovitch, T., Mitsutake, N., Mine, M., Shibata, Y., Nakashima, M.,& Yamashita, S.. (2011). Mutational and clinico-pathological analysis of papillary thyroid carcinoma in Serbia. in Endocrine Journal, 58(5), 381-393.
https://doi.org/10.1507/endocrj.K11E-054

Stanojević B, Džodić RR, Saenko V, Milovanović ZM, Pupić G, Živković O, Marković I, Đurišić I, Buta M, Dimitrijević BB, Rogounovitch T, Mitsutake N, Mine M, Shibata Y, Nakashima M, Yamashita S. Mutational and clinico-pathological analysis of papillary thyroid carcinoma in Serbia. in Endocrine Journal. 2011;58(5):381-393.
doi:10.1507/endocrj.K11E-054 .

Stanojević, Boban, Džodić, Radan R., Saenko, Vladimir, Milovanović, Zorka M., Pupić, Gordana, Živković, Ognjen, Marković, Ivan, Đurišić, Igor, Buta, Marko, Dimitrijević, Bogomir B., Rogounovitch, Tatiana, Mitsutake, Norisato, Mine, Mariko, Shibata, Yoshisada, Nakashima, Masahiro, Yamashita, Shunichi, "Mutational and clinico-pathological analysis of papillary thyroid carcinoma in Serbia" in Endocrine Journal, 58, no. 5 (2011):381-393,
https://doi.org/10.1507/endocrj.K11E-054 . .