Immunohistochemical analysis of cyclin A expression in Wilms tumor

Background Cyclin A overexpression is found in a variety of human tumors and correlates with unfavorable outcome. We analyzed immunohistochemical expression of cyclin A in Wilms tumor (WT) in relation to clinicopathological characteristics, preoperative chemotherapy (PrOpChTh), and overall survival...

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Main Authors: Sanja Radojević-Škodrić, Dimitrije Brašanac, Slaviša M. Đuričić, Sofija Glumac, Zlatibor Lončar, Ivan Pavlović, Ana Todorović, Gorana Nikolić, Ivana Baralić, Snežana Pejić
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Language:English
Published: PeerJ Inc. 2019-01-01
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Online Access:https://peerj.com/articles/6212.pdf
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author Sanja Radojević-Škodrić
Dimitrije Brašanac
Slaviša M. Đuričić
Sofija Glumac
Zlatibor Lončar
Ivan Pavlović
Ana Todorović
Gorana Nikolić
Ivana Baralić
Snežana Pejić
author_facet Sanja Radojević-Škodrić
Dimitrije Brašanac
Slaviša M. Đuričić
Sofija Glumac
Zlatibor Lončar
Ivan Pavlović
Ana Todorović
Gorana Nikolić
Ivana Baralić
Snežana Pejić
author_sort Sanja Radojević-Škodrić
collection DOAJ
description Background Cyclin A overexpression is found in a variety of human tumors and correlates with unfavorable outcome. We analyzed immunohistochemical expression of cyclin A in Wilms tumor (WT) in relation to clinicopathological characteristics, preoperative chemotherapy (PrOpChTh), and overall survival (OS). Methods This retrospective study involved 43 patients who underwent nephrectomy from January 1996 to October 2010. Tumor stage and histological subtype were determined by revised Societé International d’Oncologie Pediatrique protocol, based on histological components/alterations caused by PrOpChTh, within the prognostic group of low, intermediate and high risk, and with criteria for anaplasia. The regressive/necrotic changes in total tumor mass of primary tumor and the proportion of epithelial, blastemal, and stromal components in the remaining viable tumor tissue were also determined. Cyclin A expression was evaluated by immunohistochemistry using a polyclonal rabbit, antihuman antibody (H-432). Results Cyclin A overexpression was found in 34.3% of WTs, with higher frequency in tumors with epithelial (31.3%) and blastemal (37.1%) components than those with stromal component (17.7%). Regarding histological type, cyclin A overexpression was found most often in focal anaplasia (100%), stromal (60%), and diffuse anaplastic (66.7) WTs. The overexpression was also more frequent in stages 3 and 4 (77.8% and 66.7%, respectively) compared to tumors in stages 1 and 2 (13.3% and 12.5%, respectively; p = 0.004) in all components, as well as in blastemal component in stages 3 and 4 (77.8% and 66.7%, respectively) vs. stages 1 and 2 (13.3% and 25%, respectively, p = 0.009). Cyclin A overexpression in all components was 66.7% in WTs with metastasis and 31.3% in WTs without metastasis (p = 0.265, Fisher test). Log-rank testing revealed differences of OS regarding stage (p = 0.000), prognostic groups (p = 0.001), and cyclin A expression in blastemal component (p = 0.025). After univariate analysis, tumor stage (p = 0.001), prognostic group (p = 0.004), and cyclin A expression in blastemal component (p = 0.042) were significant prognostic factors for OS; however, after multivariate analysis, none of these factors were confirmed as independent predictors of survival. Discussion This study showed that cyclin A overexpression might be associated with the development and progression of WT with anaplasia. Also, cyclin A overexpression was more often observed in advanced stages (3 and 4) of WT, in the group of high-risk WTs, and in focal and diffuse anaplasia WTs. There was no relation of cyclin A overexpression and metastatic ability of WT. Although this study has not confirmed the prognostic value of cyclin A overexpression, its association with unfavorable prognosis should be further evaluated.
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spelling doaj.art-9faaaf3265234cce9d3f1e75b896aae72023-12-02T22:01:45ZengPeerJ Inc.PeerJ2167-83592019-01-016e621210.7717/peerj.6212Immunohistochemical analysis of cyclin A expression in Wilms tumorSanja Radojević-Škodrić0Dimitrije Brašanac1Slaviša M. Đuričić2Sofija Glumac3Zlatibor Lončar4Ivan Pavlović5Ana Todorović6Gorana Nikolić7Ivana Baralić8Snežana Pejić9Institute of Pathology, School of Medicine, University of Belgrade, Belgrade, SerbiaInstitute of Pathology, School of Medicine, University of Belgrade, Belgrade, SerbiaDepartment of Clinical Pathology, Mother and Child Health Care Institute of Serbia “Dr. Vukan Čupić”, Belgrade, SerbiaInstitute of Pathology, School of Medicine, University of Belgrade, Belgrade, SerbiaClinic for Emergency Surgery, Clinical Center of Serbia, Belgrade, SerbiaLaboratory of Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, SerbiaLaboratory of Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, SerbiaDepartment of Biomedical Engineering, Innovation Center, Faculty of Mechanical Engineering, University of Belgrade, Belgrade, SerbiaZvezdara University Medical Center, Belgrade, SerbiaLaboratory of Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, SerbiaBackground Cyclin A overexpression is found in a variety of human tumors and correlates with unfavorable outcome. We analyzed immunohistochemical expression of cyclin A in Wilms tumor (WT) in relation to clinicopathological characteristics, preoperative chemotherapy (PrOpChTh), and overall survival (OS). Methods This retrospective study involved 43 patients who underwent nephrectomy from January 1996 to October 2010. Tumor stage and histological subtype were determined by revised Societé International d’Oncologie Pediatrique protocol, based on histological components/alterations caused by PrOpChTh, within the prognostic group of low, intermediate and high risk, and with criteria for anaplasia. The regressive/necrotic changes in total tumor mass of primary tumor and the proportion of epithelial, blastemal, and stromal components in the remaining viable tumor tissue were also determined. Cyclin A expression was evaluated by immunohistochemistry using a polyclonal rabbit, antihuman antibody (H-432). Results Cyclin A overexpression was found in 34.3% of WTs, with higher frequency in tumors with epithelial (31.3%) and blastemal (37.1%) components than those with stromal component (17.7%). Regarding histological type, cyclin A overexpression was found most often in focal anaplasia (100%), stromal (60%), and diffuse anaplastic (66.7) WTs. The overexpression was also more frequent in stages 3 and 4 (77.8% and 66.7%, respectively) compared to tumors in stages 1 and 2 (13.3% and 12.5%, respectively; p = 0.004) in all components, as well as in blastemal component in stages 3 and 4 (77.8% and 66.7%, respectively) vs. stages 1 and 2 (13.3% and 25%, respectively, p = 0.009). Cyclin A overexpression in all components was 66.7% in WTs with metastasis and 31.3% in WTs without metastasis (p = 0.265, Fisher test). Log-rank testing revealed differences of OS regarding stage (p = 0.000), prognostic groups (p = 0.001), and cyclin A expression in blastemal component (p = 0.025). After univariate analysis, tumor stage (p = 0.001), prognostic group (p = 0.004), and cyclin A expression in blastemal component (p = 0.042) were significant prognostic factors for OS; however, after multivariate analysis, none of these factors were confirmed as independent predictors of survival. Discussion This study showed that cyclin A overexpression might be associated with the development and progression of WT with anaplasia. Also, cyclin A overexpression was more often observed in advanced stages (3 and 4) of WT, in the group of high-risk WTs, and in focal and diffuse anaplasia WTs. There was no relation of cyclin A overexpression and metastatic ability of WT. Although this study has not confirmed the prognostic value of cyclin A overexpression, its association with unfavorable prognosis should be further evaluated.https://peerj.com/articles/6212.pdfWilms tumorImmunohistochemistrySurvivalCyclin ARetrospective study
spellingShingle Sanja Radojević-Škodrić
Dimitrije Brašanac
Slaviša M. Đuričić
Sofija Glumac
Zlatibor Lončar
Ivan Pavlović
Ana Todorović
Gorana Nikolić
Ivana Baralić
Snežana Pejić
Immunohistochemical analysis of cyclin A expression in Wilms tumor
PeerJ
Wilms tumor
Immunohistochemistry
Survival
Cyclin A
Retrospective study
title Immunohistochemical analysis of cyclin A expression in Wilms tumor
title_full Immunohistochemical analysis of cyclin A expression in Wilms tumor
title_fullStr Immunohistochemical analysis of cyclin A expression in Wilms tumor
title_full_unstemmed Immunohistochemical analysis of cyclin A expression in Wilms tumor
title_short Immunohistochemical analysis of cyclin A expression in Wilms tumor
title_sort immunohistochemical analysis of cyclin a expression in wilms tumor
topic Wilms tumor
Immunohistochemistry
Survival
Cyclin A
Retrospective study
url https://peerj.com/articles/6212.pdf
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