Determination of Tumor Heterogeneity in Colorectal Cancers Using Heterogeneity Tissue Microarrays

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• 作者：Phillip R. Stahl ; Jessica Schnellert ; Christina Koop…
• 关键词：Tissue microarrays ; Colorectal cancer ; Heterogeneity ; p53 ; HER2
• 刊名：Pathology & Oncology Research
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：21
• 期：4
• 页码：1183-1189
• 全文大小：188 KB
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• 作者单位：Phillip R. Stahl (1) r> Jessica Schnellert (1) r> Christina Koop (1) r> Ronald Simon (1) r> Andreas Marx (1) r> Jakob R. Izbicki (2) r> Guido Sauter (1) r> Alexander Quaas (1) r>r>1. Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany r> 2. General, Visceral and Thoracic Surgery Department, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany r>
• 刊物主题：Cancer Research; Oncology; Pathology; Immunology; Biomedicine general;
• 出版者：Springer Netherlands
• ISSN：1532-2807

文摘

Cancer is often heterogeneous both on a morphological and on a genetic level. Though resected tumors are often large, molecular tumor analysis is usually restricted to one tissue block. In this project we introduce a new tool for a high-throughput heterogeneity analysis of colorectal cancer. A heterogeneity tissue microarray (TMA) was manufactured from tissues of 340 patients with colorectal cancer. For this purpose 8 different tissue spots were taken from as many different cancer blocks per patient as possible (at least 4 different blocks). Additional tissue samples from 1 to 4 corresponding lymph node metastases were added from 134 patients. The system was then validated by analysing one parameter each known for minimal (p53) or substantial (HER2) heterogeneity in colorectal cancer. P53 alterations as detected by immunohistochemistry were seen in 174 (51.3 %) of 339 analyzable primary tumors of which 23 (13.2 % of positive cases) showed a heterogeneous distribution pattern. HER2 overexpression was seen in 18 (5.4 %) of 336 evaluable tumors. HER2 amplification occurred in 6 (33.3 %) of the 18 cases with HER2 overexpression. Genomic heterogeneity was more prevalent for HER2 alterations than for p53 alterations. For immunohistochemical expression analysis, 16 of 18 positive cases were heterogeneous (88.9 %) and for amplification 3 of 6 cases (50 %) were heterogeneous. Large section validation revealed, however a considerable fraction of heterogeneous cases were due to technical artifacts. In summary, our data suggest, that heterogeneity TMAs are a powerful tool to rapidly screen for molecular heterogeneity in colorectal cancer. Keywords Tissue microarrays Colorectal cancer Heterogeneity p53 HER2