Immunohistochemical analysis of cyclin A expression in Wilms tumor

PeerJ. 2019 Jan 11:6:e6212. doi: 10.7717/peerj.6212. eCollection 2019.


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.

Keywords: Cyclin A; Immunohistochemistry; Retrospective study; Survival; Wilms tumor.

Grants and funding

This work was financially supported by the Ministry of Health, Republic of Serbia and Ministry of Education, Science and Technological Development, Republic of Serbia (Grant 175059). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.