PMID- 23887156
OWN - NLM
STAT- MEDLINE
DCOM- 20131125
LR  - 20211021
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 37
IP  - 9
DP  - 2013 Sep
TI  - ROS1 immunohistochemistry for detection of ROS1-rearranged lung adenocarcinomas.
PG  - 1441-9
LID - 10.1097/PAS.0b013e3182960fa7 [doi]
AB  - 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. In this study, we examine the correlation 
      between ROS1 IHC and FISH and describe the clinicopathologic characteristics of 
      ROS1-rearranged lung tumors. ROS1 IHC was performed using clone D4D6 on 
      whole-tissue sections. In a validation cohort, IHC was compared with ROS1 
      break-apart FISH in 53 cases of lung ACA enriched for an absence of known genetic 
      alterations and never-smoking status. In a screening cohort, we performed ROS1 
      IHC on 167 consecutive cases of lung ACA from a routine molecular diagnostic 
      practice and confirmed positive results by FISH. In the validation cohort, 6 
      cases (11%) were both FISH and IHC positive. One FISH-negative case was strongly 
      ROS1 IHC positive. All IHC-negative cases were FISH negative. In the screening 
      cohort, 2 of 167 (1.2%) had strong, diffuse ROS1 protein expression; a 
      rearrangement was confirmed by FISH in both. ROS1-translocated tumors were 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.
FAU - Sholl, Lynette M
AU  - Sholl LM
AD  - *Department of Pathology, Brigham and Women's Hospital daggerLowe Center for Thoracic 
      Oncology double daggerBelfer Institute for Applied Cancer Science, Dana Farber Cancer 
      Institute, Boston, MA.
FAU - Sun, Heather
AU  - Sun H
FAU - Butaney, Mohit
AU  - Butaney M
FAU - Zhang, Chengsheng
AU  - Zhang C
FAU - Lee, Charles
AU  - Lee C
FAU - Janne, Pasi A
AU  - Janne PA
FAU - Rodig, Scott J
AU  - Rodig SJ
LA  - eng
GR  - P50 CA090578/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (ROS1 protein, human)
SB  - IM
MH  - Adenocarcinoma/*chemistry/*genetics/mortality/pathology
MH  - Adenocarcinoma of Lung
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biopsy
MH  - Female
MH  - *Gene Rearrangement
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - *Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/*chemistry/*genetics/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Phenotype
MH  - Predictive Value of Tests
MH  - Protein-Tyrosine Kinases/*analysis/*genetics
MH  - Proto-Oncogene Proteins/*analysis/*genetics
MH  - Reproducibility of Results
PMC - PMC3831351
MID - NIHMS478707
COIS- Conflicts of Interest: For the remaining authors none were declared.
EDAT- 2013/07/28 06:00
MHDA- 2013/12/16 06:00
PMCR- 2014/09/01
CRDT- 2013/07/27 06:00
PHST- 2013/07/27 06:00 [entrez]
PHST- 2013/07/28 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - 10.1097/PAS.0b013e3182960fa7 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2013 Sep;37(9):1441-9. doi: 10.1097/PAS.0b013e3182960fa7.