Home > E. Pathology by systems > Respiratory system > Lungs > ROS1-associated lung adenocarcinoma

ROS1-associated lung adenocarcinoma

Friday 15 March 2013

ROS1-rearranged Lung Cancer; ROS1-associated pulmonary adenocarcinoma; ROS1-rearranged pulmonary carcinoma; ROS1-associated pulmonary carcinoma; ROS1-rearranged lung adenocarcinoma

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.

Open references

- ALK and ROS1 as targeted therapy paradigms and clinical implications to overcome crizotinib resistance. Ye M, Zhang X, Li N, Zhang Y, Jing P, Chang N, Wu J, Ren X, Zhang J. Oncotarget. 2016 Jan 18. doi : 10.18632/oncotarget.6935 PMID: 26802023 (Free)

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