Tsiambas Evangelos, Karameris Andreas, Tiniakos Dina G, Karakitsos Petros
Department of Pathology, Tissue Microarrays and Computerized Image Analysis Laboratories, 417 VA Hospital, Athens, Greece.
Pancreatology. 2007;7(1):45-52. doi: 10.1159/000101877. Epub 2007 Apr 18.
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.
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.
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).
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.
背景/目的：联合评估拓扑异构酶IIa（Topo IIa）蛋白表达及基因状态在胰腺导管腺癌中的情况，确定其改变的潜在预后影响。
使用组织微阵列，对50例散发的原发性胰腺导管腺癌进行两次取样，将样本重新包埋于一个直径为1毫米的石蜡块中。在连续组织切片上分别进行免疫组织化学和显色原位杂交，以检测蛋白表达水平、17号染色体及Topo IIa基因状态。最后使用半自动图像分析系统评估蛋白表达水平。
相当一部分肿瘤显示Topo IIa过表达（32/50，即64%）。分别在9例和4例中检测到基因扩增和缺失，且与蛋白过表达相关。在19/50的肿瘤中观察到17号染色体非整倍体，其与较差的生存率相关（Cox回归检验：p = 0.001）。Topo IIa蛋白表达与分期（p = 0.021）和分级（p = 0.034）密切相关。
Topo IIa基因扩增与蛋白过表达相关，但反之不成立。这对于仅根据分子失调标准而非仅免疫组化结果，将靶向化疗药物（如蒽环类药物）应用于特定患者亚组而言是一个关键观察结果。此外，17号染色体而非Topo IIa基因不稳定可作为潜在的独立预后因素。
