Hutchinson Ryan A, Adams Richard A, McArt Darragh G, Salto-Tellez Manuel, Jasani Bharat, Hamilton Peter W
Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7AE, Northern Ireland, UK.
Waring Laboratory, Department of Pathology, Centre for Translational Pathology, University of Melbourne, Parkville, 3010, VIC, Australia.
J Transl Med. 2015 Jul 7;13:217. doi: 10.1186/s12967-015-0531-z.
The treatment of cancer is becoming more precise, targeting specific oncogenic drivers with targeted molecular therapies. The epidermal growth factor receptor has been found to be over-expressed in a multitude of solid tumours. Immunohistochemistry is widely used in the fields of diagnostic and personalised medicine to localise and visualise disease specific proteins. To date the clinical utility of epidermal growth factor receptor immunohistochemistry in determining monoclonal antibody efficacy has remained somewhat inconclusive. The lack of an agreed reproducible scoring criteria for epidermal growth factor receptor immunohistochemistry has, in various clinical trials yielded conflicting results as to the use of epidermal growth factor receptor immunohistochemistry assay as a companion diagnostic. This has resulted in this test being removed from the licence for the drug panitumumab and not performed in clinical practice for cetuximab. In this review we explore the reasons behind this with a particular emphasis on colorectal cancer, and to suggest a way of resolving the situation through improving the precision of epidermal growth factor receptor immunohistochemistry with quantitative image analysis of digitised images complemented with companion molecular morphological techniques such as in situ hybridisation and section based gene mutation analysis.
癌症治疗正变得更加精准，通过靶向分子疗法针对特定的致癌驱动因素。已发现表皮生长因子受体在多种实体瘤中过度表达。免疫组织化学在诊断和个性化医学领域被广泛用于定位和可视化疾病特异性蛋白质。迄今为止，表皮生长因子受体免疫组织化学在确定单克隆抗体疗效方面的临床效用仍有些不确定。由于缺乏针对表皮生长因子受体免疫组织化学的公认可重复评分标准，在各种临床试验中，关于将表皮生长因子受体免疫组织化学检测用作伴随诊断的结果相互矛盾。这导致该检测从帕尼单抗的药物许可中被删除，并且在西妥昔单抗的临床实践中不再进行。在本综述中，我们探讨了其背后的原因，特别强调结直肠癌，并建议通过数字化图像的定量图像分析以及原位杂交和基于切片的基因突变分析等伴随分子形态学技术提高表皮生长因子受体免疫组织化学的精度来解决这一问题。
