Original Paper

Evaluation of Topoisomerase IIa Expression in Pancreatic Ductal Adenocarcinoma: A Pilot Study Using Chromogenic in situ Hybridization and Immunohistochemistry on Tissue Microarrays
Evangelos Tsiambas^a, Andreas Karameris^a, Dina G. Tiniakos^b, Petros Karakitsos<sup>b

a</sup>Department of Pathology, Tissue Microarrays and Computerized Image Analysis Laboratories, 417 VA Hospital, and
^bLaboratory of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Athens, Greece

Address of Corresponding Author

Pancreatology 2007;7:45-52 (DOI: 10.1159/000101877)

  Key Words

• Pancreatic ductal adenocarcinoma
• Tissue microarrays
• Chromogenic in situ hybridization
• Topoisomerase IIa

  Abstract

Background/Aims: To co-evaluate topoisomerase IIa (Topo IIa) protein expression and gene status in pancreatic ductal adenocarcinoma, determining the potential prognostic impact of its alterations. Methods: Using tissue microarrays, 50 sporadic, primary pancreatic ductal adenocarcinomas were cored twice and re-embedded into one paraffin block with a core diameter of 1 mm. Immunohistochemistry and chromogenic in situ hybridization were performed in serial tissue sections for the detection of protein expression levels, chromosome 17 and Topo IIa gene status, respectively. Finally using a semi-automated image analysis system we evaluated the levels of protein expression. Results: A significant proportion of the tumors showed Topo IIa overexpression (32/50 or 64%). Gene amplification and deletion were detected in 9 and 4 cases, respectively, associated with protein overexpression. Aneuploidy regarding chromosome 17 was observed in 19/50 tumors and correlated with poor survival rate (Cox regression test: p = 0.001). Topo IIa protein expression was strongly correlated with stage (p = 0.021) and grade (p = 0.034). Conclusions: Topo IIa gene amplification correlates with protein overexpression, but not vice versa. This is a crucial observation for the application of targeted chemotherapies, such as anthracyclines, only in subgroups of patients, according to molecular deregulation criteria and not only to immunohistochemical results. Also, chromosome 17 and not Topo IIa gene instability can be used as a potential independent prognostic factor.

Copyright © 2007 S. Karger AG, Basel and IAP

  Author Contacts

Capt. E. Tsiambas, MD
19B Symis Street, Ag Paraskevi
GR-15341 Athens (Greece)
Tel./Fax +30 210 729 7977, E-Mail tsiambasecyto@yahoo.gr

  Article Information

Received: October 24, 2005
Accepted: March 20, 2006
Published online: April 18, 2007
Number of Print Pages : 8
Number of Figures : 3, Number of Tables : 3, Number of References : 33