Medical School, University of Athens, Department of Pathology, 417 VA Hospital (NIMTS), Athens, Greece.
J Gastrointestin Liver Dis. 2009 Sep;18(3):293-8.
Although Epidermal Growth Factor Receptor (EGFR) over expression is a frequent event in colon adenocarcinoma (CA), identification of EGFR gene deregulation mechanisms--combined to k-ras mutations--remains the basic criterion for rational application of anti-EGFR targeted therapeutic strategies.
To detect EGFR gene numerical alterations in CA based on a combination of intra-operative imprints and the corresponding tissue microarrays.
60 paraffin embedded primary CAs were cored at 1.5 mm diameter and transferred to the final microarray block. Chromogenic in situ hybridization (CISH) was performed using EGFR gene and chromosome 7 centromeric probes in the tissue microarray and also in the corresponding intra-operative imprints.
CISH analysis detected 4/60 (6.6%) EGFR gene amplified cases, whereas chromosome 7 aneuploidy was identified in 11/60 (18.3%) cases. Significant association was established by correlating stage to chromosome 7 (p=0.024). A high value of concordance (kappa=1) was observed comparing overall gene status based on the tissue cores and the corresponding imprints, whereas EGFR/CEN 7 copies were more numerous in imprints than in tissue microarrays (p=0.03).
Intra-operative imprint cytology provides accurate and fast results in detecting EGFR gene/chromosome 7 centromeric signals by CISH due to the nuclear integrity and monolayer formation of the examined cells. Based on this molecular analysis, gastroenterologists and oncologists can handle those patients in a rational way regarding targeted therapies. Furthermore, chromosome 7 aneuploidy is associated with a more advanced stage in CA.
尽管表皮生长因子受体（EGFR）过度表达是结肠癌（CA）的常见事件，但确定 EGFR 基因失调机制——结合 k-ras 突变——仍然是合理应用抗 EGFR 靶向治疗策略的基本标准。
通过术中印迹和相应的组织微阵列组合，检测 CA 中 EGFR 基因的数值改变。
对 60 例石蜡包埋的原发性 CA 进行 1.5mm 直径的芯活检，并转移到最终的微阵列块中。在组织微阵列和相应的术中印迹中使用 EGFR 基因和染色体 7 着丝粒探针进行显色原位杂交（CISH）。
CISH 分析检测到 4/60（6.6%）EGFR 基因扩增病例，而 11/60（18.3%）病例中发现染色体 7 非整倍体。通过将阶段与染色体 7 相关联（p=0.024），建立了显著的相关性。基于组织芯和相应印迹的总体基因状态的相关性很高（kappa=1），而印迹中的 EGFR/CEN 7 拷贝数比组织微阵列中更多（p=0.03）。
由于所检查细胞的核完整性和单层形成，术中印迹细胞学通过 CISH 提供了准确和快速的结果，用于检测 EGFR 基因/染色体 7 着丝粒信号。基于这种分子分析，胃肠病学家和肿瘤学家可以根据靶向治疗对这些患者进行合理的处理。此外，染色体 7 非整倍体与 CA 的更晚期阶段相关。
