The ROS1 IHC test is a screening test. All cases considered to be positive for ROS1 IHC must be confirmed by ROS1 FISH testing in order to determine eligibility for crizotinib therapy.
Submit a formalin-fixed, parafin embedded (FFPE) tissue block
Formalin-fixed, paraffin embedded (FFPE) tissue block
FFPE tissue section mounted on a charged, unstained slide
Immunohistochemical staining and microscopic examination
Lack of staining in tumor cells. The literature recommends at least 20 tumor cells be evaluated before calling a case negative.
Examples of ROS1 IHC staining patterns 2
a) Diffuse intracytoplasmic globular reactivity
b) Focal intracytoplasmic globular reactivity
c) Reactivity localized to the lateral surface
d) Reactivity localized along the apical surface
Diffuse (a) or focal (b) instracytoplasmic globular reactivity was observed in 6 of 10 CD74-ROS1-positive cancers. Plasma membranous accentuation with a fine granular quality was observed in 3 of 4 EZR-ROS1-positive tumors; reactivity localized to the lateral surface in two cases (c) and along the apical surface in one case (d).
EZR-ROS1 positive signet-ring cell carcinoma (a) showed diffuse but only weak-moderate ROS1 immunoreactivity.
Known stain artifacts