ROS1-rearranged lung adenocarcinoma
Friday 15 March 2013
ROS1-rearranged Lung Cancer; ROS1-associated pulmonary adenocarcinoma; ROS1-rearranged pulmonary carcinoma; ROS1-associated pulmonary carcinoma
ROS1 gene rearrangements are reported in 1% to 2% of lung adenocarcinomas (ACAs) and are associated with response to the multitargeted tyrosine kinase inhibitor crizotinib.
ROS1-translocated tumors are wild type for EGFR, KRAS, and ALK and commonly had solid growth with mucinous/cribriform features and psammomatous calcification.
Recent discovery of ROS1 gene fusion in a subset of lung cancers has raised clinical interest, because ROS1 fusion-positive cancers are reportedly sensitive to kinase inhibitors.
2.5% of adenocarcinomas harbor ROS1 fusion transcripts.
The most frequent fusion partner is CD74 followed by EZR.
The affected patients are often younger non-smoking female individuals, and they had overall survival rates similar to those of the ROS1 fusion-negative cancer patients.
All the ROS1 fusion-positive tumors are adenocarcinomas except rare adenosquamous carcinomas.
Histologic examination identified an at least focal presence of either solid growth with signet-ring cells or cribriform architecture with abundant extracellular mucus in 53% of the cases.
These 2 patterns are reportedly also characteristic of anaplastic lymphoma kinase (ALK)-rearranged lung cancers, and our data suggest a phenotypic resemblance between the ROS1-rearranged and ALK-rearranged tumors.
Nearly all tumors are immunoreactive to thyroid transcription factor-1 (TTF1).
Fluorescence in situ hybridization using ROS1 break-apart probes reveals positive rearrangement signals in 23% to 93% of the tumor cells in ROS1 fusion-positive cancers.
All ROS1 fusion-positive tumors lack alteration of EGFR, KRAS, HER2, ALK, and RET genes.
Conditions for ROS1 FISH
metastatic pulmonary adenocarcinoma
others biomarkers negative: EGFR, KRAS, BRAF, HER2, ALK
ROS1 immunohistochemistry for detection of ROS1-rearranged lung adenocarcinomas. (#23887156#)
- ROS1 gene rearrangements are reported in 1% to 2% of lung adenocarcinomas (ACAs) and are associated with response to the multitargeted tyrosine kinase inhibitor crizotinib.
- ROS1 rearrangements can be detected using fluorescence in situ hybridization (FISH); however, immunohistochemistry (IHC) for ROS1 protein is a promising alternate screening modality.
- ROS1-translocated tumors are wild type for EGFR, KRAS, and ALK and commonly had solid growth with mucinous/cribriform features and psammomatous calcification.
- ROS1 protein expression in tumor cells is 100% sensitive and 92% specific for ROS1 rearrangements by FISH.
- ROS1 IHC is an effective screening tool for this rare but clinically important subset of lung ACAs.
ROS1 immunohistochemistry for detection of ROS1-rearranged lung adenocarcinomas. Sholl LM, Sun H, Butaney M, Zhang C, Lee C, Jänne PA, Rodig SJ. Am J Surg Pathol. 2013 Sep;37(9):1441-9. doi:10.1097/PAS.0b013e3182960fa7 . PMID: #23887156#
On the relevance of a testing algorithm for the detection of ROS1-rearranged lung adenocarcinomas. Mescam-Mancini L, Lantuéjoul S, Moro-Sibilot D, Rouquette I, Souquet PJ, Audigier-Valette C, Sabourin JC, Decroisette C, Sakhri L, Brambilla E, McLeer-Florin A. Lung Cancer. 2013 Dec 1. doi:10.1016/j.lungcan.2013.11.019 . PMID: #24380695#
ROS1-Rearranged Lung Cancer: A Clinicopathologic and Molecular Study of 15 Surgical Cases. Yoshida A, Kohno T, Tsuta K, Wakai S, Arai Y, Shimada Y, Asamura H, Furuta K, Shibata T, Tsuda H. Am J Surg Pathol. 2013 Apr;37(4):554-62. doi: 10.1097/PAS.0b013e3182758fe6 . PMID: #23426121#