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Topoisomerase IIalpha mRNA and protein expression in ovarian carcinoma: correlation with clinicopathological factors and prognosis.
Mod Pathol. 2009 Apr; 22(4):579-88.MP

Abstract

Topoisomerase IIalpha (Top IIalpha) is a nuclear enzyme that plays a central role in DNA metabolism, and is a molecular target for a variety of chemotherapeutic agents. Top IIalpha has recently gained attention as a biomarker for therapy response and patient survival. In this study, we attempted to assess the feasibility of measuring Top IIalpha gene expression in RNA, isolated from archival formalin-fixed paraffin-embedded tissue specimens, which are used routinely in pathology laboratories. We have employed a new technique on the basis of magnetic particles' separation and purification of nucleic acids, and evaluated both protein and mRNA expressions from the same routinely processed tissue blocks. We investigated the expression of Top IIalpha mRNA and protein by real-time reverse transcription polymerase chain reaction and immunohistochemistry, in a cohort of 133 primary ovarian carcinomas, and evaluated the association between Top IIalpha expression and clincopathological variables as well as patient outcome. Elevated Top IIalpha mRNA expression was observed in high-grade tumors (P=0.003) and advanced stage disease (P=0.011). In univariate Kaplan-Meier analysis, patients with higher expression of Top IIalpha nuclear protein had a significantly decreased overall survival (P=0.045). Interestingly, we detected cytoplasmic protein expression of Top IIalpha in a subset of samples. Cytoplasmic expression of Top IIalpha was associated with the expression of chromosomal region maintenance/exportin 1 (CRM1)-a nuclear export protein (P=0.008). Our study suggests that Top IIalpha overexpression is involved in the progression of ovarian cancer in a subset of the patients. Our results encourage the further evaluation of the prognostic and predictive values of Top IIalpha expression in ovarian carcinoma, which might help to assess the patients' risk profile, and the planning of an individualized therapy.

Authors+Show Affiliations

Institute of Pathology, Charité University Hospital, Berlin, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19270648

Citation

Faggad, Areeg, et al. "Topoisomerase IIalpha mRNA and Protein Expression in Ovarian Carcinoma: Correlation With Clinicopathological Factors and Prognosis." Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, vol. 22, no. 4, 2009, pp. 579-88.
Faggad A, Darb-Esfahani S, Wirtz R, et al. Topoisomerase IIalpha mRNA and protein expression in ovarian carcinoma: correlation with clinicopathological factors and prognosis. Mod Pathol. 2009;22(4):579-88.
Faggad, A., Darb-Esfahani, S., Wirtz, R., Sinn, B., Sehouli, J., Könsgen, D., Lage, H., Weichert, W., Noske, A., Budczies, J., Müller, B. M., Buckendahl, A. C., Röske, A., Eldin Elwali, N., Dietel, M., & Denkert, C. (2009). Topoisomerase IIalpha mRNA and protein expression in ovarian carcinoma: correlation with clinicopathological factors and prognosis. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 22(4), 579-88. https://doi.org/10.1038/modpathol.2009.14
Faggad A, et al. Topoisomerase IIalpha mRNA and Protein Expression in Ovarian Carcinoma: Correlation With Clinicopathological Factors and Prognosis. Mod Pathol. 2009;22(4):579-88. PubMed PMID: 19270648.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Topoisomerase IIalpha mRNA and protein expression in ovarian carcinoma: correlation with clinicopathological factors and prognosis. AU - Faggad,Areeg, AU - Darb-Esfahani,Silvia, AU - Wirtz,Ralph, AU - Sinn,Bruno, AU - Sehouli,Jalid, AU - Könsgen,Dominique, AU - Lage,Hermann, AU - Weichert,Wilko, AU - Noske,Aurelia, AU - Budczies,Jan, AU - Müller,Berit M, AU - Buckendahl,Ann-Christin, AU - Röske,Annika, AU - Eldin Elwali,Nasr, AU - Dietel,Manfred, AU - Denkert,Carsten, Y1 - 2009/03/06/ PY - 2009/3/10/entrez PY - 2009/3/10/pubmed PY - 2009/7/16/medline SP - 579 EP - 88 JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JO - Mod Pathol VL - 22 IS - 4 N2 - Topoisomerase IIalpha (Top IIalpha) is a nuclear enzyme that plays a central role in DNA metabolism, and is a molecular target for a variety of chemotherapeutic agents. Top IIalpha has recently gained attention as a biomarker for therapy response and patient survival. In this study, we attempted to assess the feasibility of measuring Top IIalpha gene expression in RNA, isolated from archival formalin-fixed paraffin-embedded tissue specimens, which are used routinely in pathology laboratories. We have employed a new technique on the basis of magnetic particles' separation and purification of nucleic acids, and evaluated both protein and mRNA expressions from the same routinely processed tissue blocks. We investigated the expression of Top IIalpha mRNA and protein by real-time reverse transcription polymerase chain reaction and immunohistochemistry, in a cohort of 133 primary ovarian carcinomas, and evaluated the association between Top IIalpha expression and clincopathological variables as well as patient outcome. Elevated Top IIalpha mRNA expression was observed in high-grade tumors (P=0.003) and advanced stage disease (P=0.011). In univariate Kaplan-Meier analysis, patients with higher expression of Top IIalpha nuclear protein had a significantly decreased overall survival (P=0.045). Interestingly, we detected cytoplasmic protein expression of Top IIalpha in a subset of samples. Cytoplasmic expression of Top IIalpha was associated with the expression of chromosomal region maintenance/exportin 1 (CRM1)-a nuclear export protein (P=0.008). Our study suggests that Top IIalpha overexpression is involved in the progression of ovarian cancer in a subset of the patients. Our results encourage the further evaluation of the prognostic and predictive values of Top IIalpha expression in ovarian carcinoma, which might help to assess the patients' risk profile, and the planning of an individualized therapy. SN - 1530-0285 UR - https://www.unboundmedicine.com/medline/citation/19270648/Topoisomerase_IIalpha_mRNA_and_protein_expression_in_ovarian_carcinoma:_correlation_with_clinicopathological_factors_and_prognosis_ L2 - https://doi.org/10.1038/modpathol.2009.14 DB - PRIME DP - Unbound Medicine ER -