PMID- 22134072
OWN - NLM
STAT- MEDLINE
DCOM- 20120504
LR  - 20220409
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Print)
IS  - 1556-0864 (Linking)
VI  - 7
IP  - 1
DP  - 2012 Jan
TI  - Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma.
PG  - 90-7
LID - 10.1097/JTO.0b013e31823c5c32 [doi]
AB  - INTRODUCTION: The EML4-anaplastic lymphoma kinase (ALK) translocation is a 
      recognized oncogenic driver in non-small cell lung cancer. We investigated 
      immunohistochemistry (IHC) screening with fluorescence in situ hybridization 
      (FISH) confirmation for ALK detection and estimated the prevalence of ALK 
      positivity in our patient cohort of never-smokers, together with differences in 
      clinical outcomes and prognostic factors for patients with ALK-positive and 
      ALK-negative tumors. METHODS: We designed a three-phase study (training, 
      validation, and testing) in 300 never-smokers with lung adenocarcinoma from the 
      observational Mayo Clinic Lung Cancer Cohort. Tumor samples were tested using IHC 
      and FISH, and concordance between the methods was assessed. Clinical outcomes 
      were assessed via 5-year progression- or recurrence-free survival from diagnosis. 
      Prognostic factors for ALK-positive tumors and metastases were also investigated. 
      RESULTS: ALK-positive patients were significantly (p < 0.05) younger and had 
      higher grade tumors than ALK-negative patients. ALK positivity was 12.2% by IHC 
      and confirmed at 8.2% of tumors by FISH, with complete concordance between IHC 
      3+/0 and FISH+/- assessments, respectively. Five-year risk of progression or 
      recurrence was doubled for patients with ALK-positive compared with ALK-negative 
      tumors; ALK-positive tumors also appeared to be associated with a higher risk of 
      brain and liver metastases. CONCLUSIONS: Our findings suggest that ALK positivity 
      is associated with a significantly poor outcome in nonsmoking-related 
      adenocarcinoma and that ALK-positive tumors may be associated with an increased 
      risk of brain and liver metastases compared with ALK-negative disease. 
      Consequently, an unmet medical need exists in ALK-positive lung cancer patients, 
      and effective ALK-specific therapies are needed.
FAU - Yang, Ping
AU  - Yang P
AD  - Division of Epidemiology, Health Sciences Research, Mayo Clinic, Rochester, 
      Minnesota 55905, USA. yang.ping@mayo.edu
FAU - Kulig, Kimary
AU  - Kulig K
FAU - Boland, Jennifer M
AU  - Boland JM
FAU - Erickson-Johnson, Michele R
AU  - Erickson-Johnson MR
FAU - Oliveira, Andre M
AU  - Oliveira AM
FAU - Wampfler, Jason
AU  - Wampfler J
FAU - Jatoi, Aminah
AU  - Jatoi A
FAU - Deschamps, Claude
AU  - Deschamps C
FAU - Marks, Randolph
AU  - Marks R
FAU - Fortner, Connie
AU  - Fortner C
FAU - Stoddard, Shawn
AU  - Stoddard S
FAU - Nichols, Francis
AU  - Nichols F
FAU - Molina, Julian
AU  - Molina J
FAU - Aubry, Marie-Christine
AU  - Aubry MC
FAU - Tang, Hui
AU  - Tang H
FAU - Yi, Eunhee S
AU  - Yi ES
LA  - eng
GR  - R01 CA115857/CA/NCI NIH HHS/United States
GR  - R01 CA084354/CA/NCI NIH HHS/United States
GR  - R01 CA 80127/CA/NCI NIH HHS/United States
GR  - R01 CA080127/CA/NCI NIH HHS/United States
GR  - R01 CA 84354/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Adenocarcinoma/*genetics/*secondary
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anaplastic Lymphoma Kinase
MH  - Brain Neoplasms/*secondary
MH  - Disease Progression
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Liver Neoplasms/*secondary
MH  - Lung Neoplasms/*genetics/*pathology
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Receptor Protein-Tyrosine Kinases/*genetics
MH  - Smoking
MH  - Young Adult
PMC - PMC3931519
MID - NIHMS546661
COIS- Conflicts of interest: KK is an employee of Pfizer, Inc.
EDAT- 2011/12/03 06:00
MHDA- 2012/05/05 06:00
PMCR- 2014/02/21
CRDT- 2011/12/03 06:00
PHST- 2011/12/03 06:00 [entrez]
PHST- 2011/12/03 06:00 [pubmed]
PHST- 2012/05/05 06:00 [medline]
PHST- 2014/02/21 00:00 [pmc-release]
AID - S1556-0864(15)31764-0 [pii]
AID - 10.1097/JTO.0b013e31823c5c32 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2012 Jan;7(1):90-7. doi: 10.1097/JTO.0b013e31823c5c32.