PMID- 25514802
OWN - NLM
STAT- MEDLINE
DCOM- 20151208
LR  - 20220321
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 10
IP  - 4
DP  - 2015 Apr
TI  - ALK testing in lung adenocarcinoma: technical aspects to improve FISH evaluation 
      in daily practice.
PG  - 595-602
LID - 10.1097/JTO.0000000000000444 [doi]
AB  - INTRODUCTION: Anaplastic lymphoma kinase (ALK) gene rearrangement characterizes a 
      subgroup of patients with lung adenocarcinoma who may benefit from ALK 
      inhibitors. Fluorescence in situ hybridization (FISH) with a 
      break-apart/split-signal strategy is the gold standard to investigate ALK. The 
      cutoff to define ALK positivity has been settled at 15% or greater. A subset of 
      patients has ALK borderline status, showing 15% +/- 5% positive cells. Several 
      aspects, both biological and technical, might influence signals evaluation, 
      making FISH interpretation a challenging task. To improve ALK evaluation, we 
      classified the different FISH patterns on the basis of the type of the split 
      signals, namely short, long, far away, and deleted. METHODS: We investigated ALK 
      gene status by FISH in 244 lung adenocarcinomas and in a series of ALK negative 
      cell lines samples, collected in three Institutions. RESULTS: ALK positive 
      profile was found in 12% of patients; long, deleted, and far-away splits were the 
      primary patterns observed. ALK borderline profile characterized 10% of samples; 
      long and deleted splits were significantly more frequent in those borderline 
      finally classified as ALK positive, whereas short split were mostly detected in 
      those borderline patients finally classified as ALK negative (p = 3.4 x 10). In 
      the ALK negative control series, short split was the predominant pattern. 
      Concordance was observed among different operators and probes for both samples 
      and controls. CONCLUSIONS: Difficulties in ALK FISH signal interpretation might 
      be bypassed using this detailed scoring system, which is highly reproducible, 
      helps clarify borderline samples (according to split type), and provides 
      experimental evidence that 15% is a reasonable cutoff to overcome the 
      assay-dependent background noise.
FAU - Martin, Vittoria
AU  - Martin V
AD  - *Institute of Pathology, Locarno, Switzerland; Departments of daggerSurgical and 
      Morphological Sciences and  section signDepartment of Pathology, Ospedale di Circolo, Varese, 
      Italy; and double daggerDepartment of Molecular and Translational Medicine, Section of 
      Pathology, School of Medicine, University of Brescia, Brescia, Italy.
FAU - Bernasconi, Barbara
AU  - Bernasconi B
FAU - Merlo, Elisabetta
AU  - Merlo E
FAU - Balzarini, Piera
AU  - Balzarini P
FAU - Vermi, William
AU  - Vermi W
FAU - Riva, Alice
AU  - Riva A
FAU - Chiaravalli, Anna Maria
AU  - Chiaravalli AM
FAU - Frattini, Milo
AU  - Frattini M
FAU - Sahnane, Nora
AU  - Sahnane N
FAU - Facchetti, Fabio
AU  - Facchetti F
FAU - Mazzucchelli, Luca
AU  - Mazzucchelli L
FAU - Sessa, Fausto
AU  - Sessa F
FAU - Tibiletti, Maria Grazia
AU  - Tibiletti MG
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
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  - 0 (DNA, Neoplasm)
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
CIN - J Thorac Oncol. 2015 Apr;10(4):548-50. PMID: 25789831
MH  - Adenocarcinoma/diagnosis/enzymology/*genetics
MH  - Adenocarcinoma of Lung
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anaplastic Lymphoma Kinase
MH  - DNA, Neoplasm/analysis/*genetics
MH  - Female
MH  - Gene Rearrangement
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Lung Neoplasms/diagnosis/enzymology/*genetics
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Prognosis
MH  - Receptor Protein-Tyrosine Kinases/*genetics/metabolism
MH  - Reproducibility of Results
MH  - Retrospective Studies
EDAT- 2014/12/17 06:00
MHDA- 2015/12/15 06:00
CRDT- 2014/12/17 06:00
PHST- 2014/12/17 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - S1556-0864(15)32361-3 [pii]
AID - 10.1097/JTO.0000000000000444 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2015 Apr;10(4):595-602. doi: 10.1097/JTO.0000000000000444.