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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.

Synopsis

- 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
- non-smoking patient
- others biomarkers negative: EGFR, KRAS, BRAF, HER2, ALK

ROS1 immunochemistry

- 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.

References

- 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