Trejo Bittar Humberto E, Luvison Alyssa, Miller Caitlyn, Dacic Sanja
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Histopathology. 2017 Aug;71(2):269-277. doi: 10.1111/his.13215. Epub 2017 May 5.
The 2013 College of American Pathologists, the Association for Molecular Pathology and the International Association for the Study of Lung Cancer guideline for EGFR and ALK testing in lung carcinoma indicates that either the primary tumour or the metastasis is suitable for testing. The heterogeneity of gene mutations has been studied extensively, while similar reports on gene rearrangements are limited. The aim of this study was to determine if ALK status between primary tumour and matched metastasis differs.
Fifteen ALK fluorescence in-situ hybridization (FISH) rearranged and 19 non-ALK FISH rearranged adenocarcinomas were collected retrospectively based on availability of tissue from a matched metastatic site. Sixty-eight samples were tested by ALK FISH (Vysis ALK break-apart FISH kit) and ALK immunohistochemistry (IHC) (Ventana ALK D5F3 CDx assay). Overall agreement of FISH and IHC was 88%, with IHC showing 100% specificity and 71% sensitivity. Concordance between primary site and metastasis by ALK FISH was seen in 30 cases (88%), and in 32 cases (94%) by ALK IHC. Five discordant cases were found (15%). Three ALK FISH discordant cases had low percentage of ALK FISH-positive tumour cells (average 23%, range: 18-31%) and all were negative by ALK IHC. One IHC discordant case had a high percentage of ALK FISH-positive tumour cells (67%), and was ALK IHC-negative. One FISH discordant case showed ALK FISH- and ALK IHC-positive primary tumour, but ALK FISH- and ALK IHC-negative metastasis.
ALK FISH results show more frequent discordances between primary tumour and matched metastases than ALK IHC, due probably to technical challenges and sample quality. This observation indicates that the quality of sample and technical expertise of the laboratory should guide the decision about ALK testing in clinical practice.
2013年美国病理学家学会、分子病理学协会及国际肺癌研究协会发布的肺癌表皮生长因子受体（EGFR）和间变性淋巴瘤激酶（ALK）检测指南指出，原发性肿瘤或转移灶均适合进行检测。基因突变的异质性已得到广泛研究，而关于基因重排的类似报告却很有限。本研究的目的是确定原发性肿瘤与配对转移灶之间的ALK状态是否存在差异。
基于配对转移部位组织的可获得性，回顾性收集了15例ALK荧光原位杂交（FISH）重排和19例非ALK FISH重排的腺癌。68个样本通过ALK FISH（Vysis ALK断裂分离FISH试剂盒）和ALK免疫组化（IHC）（Ventana ALK D5F3 CDx检测法）进行检测。FISH和IHC的总体一致性为88%，其中IHC显示出100%的特异性和71%的敏感性。ALK FISH显示原发性部位与转移灶之间的一致性在30例（88%）中可见，ALK IHC显示一致性的有32例（94%）。发现5例不一致的病例（15%）。3例ALK FISH不一致的病例中，ALK FISH阳性肿瘤细胞的比例较低（平均23%，范围：18 - 31%），且所有病例通过ALK IHC检测均为阴性。1例IHC不一致的病例中，ALK FISH阳性肿瘤细胞的比例较高（67%），且ALK IHC检测为阴性。1例FISH不一致的病例显示原发性肿瘤ALK FISH和ALK IHC均为阳性，但转移灶ALK FISH和ALK IHC均为阴性。
由于技术挑战和样本质量问题，ALK FISH结果显示原发性肿瘤与配对转移灶之间的不一致情况比ALK IHC更为常见。这一观察结果表明，样本质量和实验室的技术专业水平应指导临床实践中关于ALK检测的决策。
