A genomic and clinicopathological study of non‐small‐cell lung cancers with discordant ROS1 gene status by fluorescence in‐situ hybridisation and immunohistochemical analysis

Abstract

Compared with ROS1-rearranged cases, ROS1-discordant patients showed distinct clinical and morphological features and often harboured another oncogenic driver alteration. The use of optimised screening criteria will increase the specificity of ROS1 antibody.

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

“…Unquestionable ROS1 IHC expression (i.e., even strong but focal) with D4D6 has been described in ROS1-nonrearranged cases containing other druggable alterations (mainly EGFR mutations, but also KRAS mutations, BRAF mutations, ALK receptor tyrosine kinase gene [ALK] fusions, and erb-b2 receptor tyrosine kinase 2 gene [HER2] abnormalities), and we have had anecdotal analogous experience with SP384 (E. Conde, unpublished observation, 2019). [14][15][16]25,30,33,34 Therefore, it is not surprising that the analytical comparison data of SP384 versus FISH released by the manufacturer achieves the best balance between negative and positive agreement at the 50% cutoff, a result similar to that of our ROC curve analyses. 35 Nonetheless, the interreader precision of SP384 has been reported as high even with use of a lower cutoff (30%), so higher cutoffs should not be an interpretation challenge in the real clinical world.…”

“…11,15 Along these lines, positivity with D4D6 has been described in ROS1nonrearranged tumors having lepidic patterns of growth or containing EGFR mutations (see the next paragraph). 14,30 This potentially confounding situation could be used to our advantage when searching for external positive controls.…”

Updated guidelines for predictive biomarker testing in advanced non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

“…Moreover, it is important to consider that ROS1 expression without underlying rearrangement (false positives) has been described in nearly a third of tumours [41,42]. The presence of other molecular abnormalities, such as EGFR, KRAS, BRAF or HER2 mutations and ALK rearrangements, has also been identified in some of these tumours [43]. • Regarding FISH, usually considered as the gold-standard technique, the use of a dual-colour break-apart probes and a count of at least 50 tumour cells is recommended 1 3 [22,[38][39][40].…”

Evaluation of DNA and RNA quality from archival formalin‐fixed paraffin‐embedded tissue for next‐generation sequencing – Retrospective study in Japanese single institution

“…[5][6][7][8][9] As the evaluation of gene abnormalities by IHC is limited, genetic analysis methods, such as fluorescence in situ hybridization and polymerase chain reaction (PCR), have been increasingly used in the detection of point mutations, insertion/deletions, and formation of fusion genes. [10][11][12][13][14][15][16][17][18][19][20] In addition, there are diverse types of cancer-specific target molecules, and a large number of molecular target drugs have been developed and used clinically. Hence, cancer prognosis has significantly improved.…”