Houang Michelle, Toon Christopher W, Clarkson Adele, Sioson Loretta, de Silva Keshani, Watson Nicole, Singh Nisha R, Chou Angela, Gill Anthony J
*Cancer Diagnosis and Pathology Group, Northern Translational Cancer Research Unit, Kolling Institute of Medical Research ∥Department of Cytogenetics, PaLMS, Royal North Shore Hospital †Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards ‡Sydney Medical School, University of Sydney, Sydney §HistoPath Pathology, North Ryde ¶Department of Anatomical Pathology, SYDPATH, St Vincent's Hospital, Darlinghurst, NSW, Australia.
Appl Immunohistochem Mol Morphol. 2015 Feb;23(2):134-8. doi: 10.1097/PAI.0000000000000025.
Crizotinib, a small molecule tyrosine kinase inhibitor, has shown tremendous promise in the treatment of lung adenocarcinomas harboring either ALK or ROS1 rearrangements. Recently, small studies of colorectal carcinomas (CRCs) have suggested an incidence of EML4-ALK translocations of 0.4% to 2.4% and FIG-ROS1 translocations of 0.8%. In lung cancer, screening immunohistochemical staining for ALK and ROS1 has been validated as highly sensitive for these translocations, but this has not been investigated in CRC. We therefore sought to investigate the incidence of ALK and ROS1 overexpression as detected by immunohistochemical staining in a large cohort of CRCs. Of the 1889 CRCs, only 1 case (0.05%) demonstrated diffuse strong positive staining for ALK, whereas 14 (0.7%) showed weak nonspecific staining; the remainder were negative. The 1 positive case was confirmed to harbor an ALK rearrangement by fluorescent in situ hybridization (FISH), whereas the 14 tumors with weak staining were FISH-negative. The ALK positive case demonstrated positive expression in all dysplastic and malignant cells indicating that the translocation was an early clonal event. No cases were positive for ROS1 by immunohistochemical staining, although 2 cases did show some nonspecific staining and were shown to be negative for ROS1 translocation by FISH. We conclude that although diffuse strong positive staining for ALK is likely to be highly specific for ALK rearrangement in CRC, both ALK and ROS1 immunohistochemical staining are very low-yield tests and difficult to justify in the routine clinical setting.
克唑替尼是一种小分子酪氨酸激酶抑制剂，在治疗携带ALK或ROS1重排的肺腺癌方面显示出巨大前景。最近，针对结直肠癌（CRC）的小型研究表明，EML4-ALK易位的发生率为0.4%至2.4%，FIG-ROS1易位的发生率为0.8%。在肺癌中，针对ALK和ROS1的筛查免疫组化染色已被证实对这些易位具有高度敏感性，但在结直肠癌中尚未对此进行研究。因此，我们试图在一大群结直肠癌患者中，研究通过免疫组化染色检测到的ALK和ROS1过表达的发生率。在1889例结直肠癌中，只有1例（0.05%）ALK呈弥漫性强阳性染色，而14例（0.7%）呈弱阳性非特异性染色；其余均为阴性。通过荧光原位杂交（FISH）证实1例阳性病例存在ALK重排，而14例弱阳性染色的肿瘤FISH检测为阴性。ALK阳性病例在所有发育异常和恶性细胞中均呈阳性表达，表明该易位是一个早期克隆事件。免疫组化染色未发现ROS1阳性病例，尽管有2例显示出一些非特异性染色，FISH检测显示ROS1易位为阴性。我们得出结论，虽然ALK弥漫性强阳性染色在结直肠癌中可能对ALK重排具有高度特异性，但ALK和ROS1免疫组化染色的阳性率都非常低，在常规临床环境中难以成为合理的检测手段。
