TY  - JOUR
AU  - Glumac, Sofija
AU  - Davidović, Radoslav S.
AU  - Dožić, Branko
AU  - Hinić, Sasa
AU  - Pavlović, Ivan
AU  - Drakulić, Dunja R.
AU  - Todorović, Ana
AU  - Medojević Pavlović, Maja
AU  - Radojević-Škodrić, Sanja
AU  - Baralić, Ivana
AU  - Sopta, Jelena
AU  - Pejić, Snežana
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9887
AB  - Rhabdomyosarcoma (RMS) is a highly malignant cancer and is the most common soft tissue sarcoma in children and adolescents, but it is rare in adults (<1% of all adult malignancies). Altered expression and molecular abnormalities of cell-cycle-regulatory proteins are one of the most prominent features in RMS. Therefore, we evaluated the expression of cyclin-dependent kinase inhibitors p57 and p16, as well as p16 methylation status, along with clinicopathological characteristics and overall survival (OS) in RMS patients. This analysis was conducted on 23 pediatric and 44 adult patients. There was a male predominance in both groups and extremities were the most frequent tumor site. In adults, alveolar and pleomorphic types were almost equally represented. The majority of pediatric tumors were low grade, whereas, in adults, only one patient had a low-grade tumor. Seven pediatric (30.43%) and eight adult (18.18%) patients had a low p16 expression. The analysis of methylation status of the p16 promoter showed the presence of methylated allele only in one sample with pleomorphic histology. Six (26.1%) pediatric and 15 (34.1%) adult patients had low p57 expression, while in 17 (73.9%) pediatric and 29 (65.9%) adult patients it was assessed as high. Ninetyone percent of the pediatric patients and 32.6% of adults were alive at the end of the observational period. In adults, significant associations were found between OS and age (P = 0.020), gender (P = 0.027), tumor size (P < 0.001), lymph node status (P < 0.001), presence of metastases (P = 0.015), and p57 expression (P = 0.039). Stratification by histological type showed the correlation of low p57 expression (P = 0.030) and worse OS of patients with alveolar RMS. Univariate analysis identified age > 50 yrs. (HR 2.447), tumors > 5 cm (HR 21.31), involvement of regional lymph nodes (HR 3.96), the presence of metastases (HR 2.53), and low p57 expression (HR 2.11) as predictors of lower OS. Tumor size, regional lymph nodes involvement, and metastases were the independent predictors after multivariate analysis, while p57 did not predict OS in an independent way. In summary, although p57 was not confirmed to be an independent predictor of OS, our results indicate that its low expression may be the marker of aggressive phenotype and poor prognosis in adult RMS patients. Also, our findings suggest that epigenetic inactivation of p16 is not important in the pathogenesis of rhabdomyosarcoma.
T2  - Pathology - Research and Practice
T1  - Immunohistochemical expression of cyclin-dependent kinase inhibitors p16 and p57 in rhabdomyosarcoma
VL  - 225
SP  - 153558
DO  - 10.1016/j.prp.2021.153558
ER  - 

@article{
author = "Glumac, Sofija and Davidović, Radoslav S. and Dožić, Branko and Hinić, Sasa and Pavlović, Ivan and Drakulić, Dunja R. and Todorović, Ana and Medojević Pavlović, Maja and Radojević-Škodrić, Sanja and Baralić, Ivana and Sopta, Jelena and Pejić, Snežana",
year = "2021",
abstract = "Rhabdomyosarcoma (RMS) is a highly malignant cancer and is the most common soft tissue sarcoma in children and adolescents, but it is rare in adults (<1% of all adult malignancies). Altered expression and molecular abnormalities of cell-cycle-regulatory proteins are one of the most prominent features in RMS. Therefore, we evaluated the expression of cyclin-dependent kinase inhibitors p57 and p16, as well as p16 methylation status, along with clinicopathological characteristics and overall survival (OS) in RMS patients. This analysis was conducted on 23 pediatric and 44 adult patients. There was a male predominance in both groups and extremities were the most frequent tumor site. In adults, alveolar and pleomorphic types were almost equally represented. The majority of pediatric tumors were low grade, whereas, in adults, only one patient had a low-grade tumor. Seven pediatric (30.43%) and eight adult (18.18%) patients had a low p16 expression. The analysis of methylation status of the p16 promoter showed the presence of methylated allele only in one sample with pleomorphic histology. Six (26.1%) pediatric and 15 (34.1%) adult patients had low p57 expression, while in 17 (73.9%) pediatric and 29 (65.9%) adult patients it was assessed as high. Ninetyone percent of the pediatric patients and 32.6% of adults were alive at the end of the observational period. In adults, significant associations were found between OS and age (P = 0.020), gender (P = 0.027), tumor size (P < 0.001), lymph node status (P < 0.001), presence of metastases (P = 0.015), and p57 expression (P = 0.039). Stratification by histological type showed the correlation of low p57 expression (P = 0.030) and worse OS of patients with alveolar RMS. Univariate analysis identified age > 50 yrs. (HR 2.447), tumors > 5 cm (HR 21.31), involvement of regional lymph nodes (HR 3.96), the presence of metastases (HR 2.53), and low p57 expression (HR 2.11) as predictors of lower OS. Tumor size, regional lymph nodes involvement, and metastases were the independent predictors after multivariate analysis, while p57 did not predict OS in an independent way. In summary, although p57 was not confirmed to be an independent predictor of OS, our results indicate that its low expression may be the marker of aggressive phenotype and poor prognosis in adult RMS patients. Also, our findings suggest that epigenetic inactivation of p16 is not important in the pathogenesis of rhabdomyosarcoma.",
journal = "Pathology - Research and Practice",
title = "Immunohistochemical expression of cyclin-dependent kinase inhibitors p16 and p57 in rhabdomyosarcoma",
volume = "225",
pages = "153558",
doi = "10.1016/j.prp.2021.153558"
}

Glumac, S., Davidović, R. S., Dožić, B., Hinić, S., Pavlović, I., Drakulić, D. R., Todorović, A., Medojević Pavlović, M., Radojević-Škodrić, S., Baralić, I., Sopta, J.,& Pejić, S.. (2021). Immunohistochemical expression of cyclin-dependent kinase inhibitors p16 and p57 in rhabdomyosarcoma. in Pathology - Research and Practice, 225, 153558.
https://doi.org/10.1016/j.prp.2021.153558

Glumac S, Davidović RS, Dožić B, Hinić S, Pavlović I, Drakulić DR, Todorović A, Medojević Pavlović M, Radojević-Škodrić S, Baralić I, Sopta J, Pejić S. Immunohistochemical expression of cyclin-dependent kinase inhibitors p16 and p57 in rhabdomyosarcoma. in Pathology - Research and Practice. 2021;225:153558.
doi:10.1016/j.prp.2021.153558 .

Glumac, Sofija, Davidović, Radoslav S., Dožić, Branko, Hinić, Sasa, Pavlović, Ivan, Drakulić, Dunja R., Todorović, Ana, Medojević Pavlović, Maja, Radojević-Škodrić, Sanja, Baralić, Ivana, Sopta, Jelena, Pejić, Snežana, "Immunohistochemical expression of cyclin-dependent kinase inhibitors p16 and p57 in rhabdomyosarcoma" in Pathology - Research and Practice, 225 (2021):153558,
https://doi.org/10.1016/j.prp.2021.153558 . .