Wedden Sarah, Miller Keith, Frayling Ian M, Thomas Teresa, Chefani Alina, Miller Karolina, Hamblin Angela, Taylor Jenny C, D'Arrigo Corrado
CADQAS CIC, Poundbury Cancer Institute.
UK NEQAS Immunocytochemistry & In-Situ Hybridisation, London.
Appl Immunohistochem Mol Morphol. 2019 Jul;27(6):e54-e62. doi: 10.1097/PAI.0000000000000631.
Colorectal cancer (CRC) has many subtypes with different prognoses and response to treatment. Patients must be characterized to access the most appropriate treatment and improve outcomes. An increasing number of biomarkers are required for characterization but are not in routine use. We investigated whether CRC can be stratified routinely within a small district general hospital to inform clinical decision making at local multidisciplinary team meeting/tumor board level. We evaluated mismatch repair (MMR) and EGFR signaling pathways using predominantly in-house immunohistochemical (IHC) tests (MSH2, MSH6, MLH1, PMS2, BRAF-V600E, Her2, PTEN, cMET) as well as send away PCR/NGS tests (NRAS, KRAS, and BRAF). We demonstrated that many of the tests required for personalized treatment of CRC can be done locally and timely. Send away tests need to be requested shortly after cut-up and this needs to be firmly established in the tissue pathways for the results to be considered at multidisciplinary team meeting/tumor board. We have shown that MMR IHC combined with BRAFV600E IHC is practical and easy to perform in a small district general hospital, has full concordance with DNA-based tests and satisfies the latest NICE requirements for the identification of potential Lynch syndrome patients. We provide a framework for the interpretation and presentation of test results. It is a practical classification that clinical pathologists can use to communicate effectively with the clinical team. It is broadly based on molecular subtyping, firmly focused on treatment decisions and dependent on the panel of molecular tests currently available.
结直肠癌（CRC）有多种亚型，其预后和对治疗的反应各不相同。必须对患者进行特征描述，以便获得最合适的治疗并改善治疗结果。特征描述需要越来越多的生物标志物，但这些标志物尚未常规使用。我们调查了在一家小型地区综合医院内是否可以对结直肠癌进行常规分层，以便在当地多学科团队会议/肿瘤委员会层面为临床决策提供依据。我们主要使用内部免疫组织化学（IHC）检测（MSH2、MSH6、MLH1、PMS2、BRAF-V600E、Her2、PTEN、cMET）以及外送的PCR/NGS检测（NRAS、KRAS和BRAF）来评估错配修复（MMR）和EGFR信号通路。我们证明，结直肠癌个体化治疗所需的许多检测可以在当地及时完成。外送检测需要在标本切割后不久就提出申请，并且需要在组织流程中明确规定，以便在多学科团队会议/肿瘤委员会上考虑检测结果。我们已经表明，MMR IHC联合BRAFV600E IHC在小型地区综合医院中切实可行且易于操作，与基于DNA的检测完全一致，并满足最新的英国国家卫生与临床优化研究所（NICE）对潜在林奇综合征患者识别的要求。我们提供了一个检测结果解读和呈现的框架。这是一种临床病理学家可用于与临床团队有效沟通的实用分类方法。它广泛基于分子亚型分类，坚定地聚焦于治疗决策，并依赖于当前可用的分子检测组合。
