Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
Table 1 Clinicopathologic features and genes status of ROS1 IHC/RT-PCR
positive patients
Gender Age Smoking
TTF1/
P63
E/k/
B/
P/
H
A/R
p1 Male 55 Smoker +/- WT WT
Therapy
Efficacy
crizotinib
p2 Female 60 Never +/- WT WT No
P3 Male 62 Never +/- WT WT
PEM
+CIS
PR
PR
PFS/
Follow
-up
10m+/
alive
1m/
Dead
9m+/
alive
E/K/B/P/H: EGFR/KRAS/BRAF/PIK3CA/HER-2 20 exon mutation, A/R: ALK/
RET fusion, WT: wild type, PEM+CIS: Pemetrexed plus Cisplatin,PR: partial
response, m: months
Keywords: non-small cell lung cancer, ros1, Immunohistochemistry, RT-PCR
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
MONDAY, DECEMBER 5, 2016
P1.02-004 A RETROSPECTIVE ANALYSIS OF FREQUENCY OF ALK
GENE REARRANGEMENT IN SAUDI LUNG PATIENTS
Fouad Al Dayel 1 , Shamayel Mohammed 2 , Asma Tulbah 2 , Hamad Al Husaini 3
1 Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research
Centre, Riyadh/Saudi Arabia, 2 Pathology and Laboratory Medicine, King Faisal
Specialist Hospital and Research Center, Riyadh/Saudi Arabia, 3 Oncology Center,
King Faisal Specialist Hospital and Research Center, Riyadh/Saudi Arabia
Background: Lung carcinoma represents 2.9% of cancers seen at King Faisal
Specialist Hospital and Research Centre (KFSH&RC) as per KFSH&RC Tumor
Registry (2013), and 4% of cancers in Saudi Arabia as per National Cancer
Registry (2010). EML4-ALK re-arrangement play an important oncogenic
driver role in lung adenocarcinoma tumorgenesis in 3-5% of cases. ALK gene
rearrangement (inversion in chromosome 2) testing can identify patients with
adenocarcinoma who are sensitive to ALK tyrosine kinase inhibitors. No data
is available on the prevalence of ALK rearrangement changes in Saudi lung
cancer patients. The aim of this study is to evaluate the prevalence of ALK
gene rearrangement in lung adenocarcinoma of Saudi patients. Methods: A
total of 172 cases of lung adenocarcinoma diagnosed at KFSH&RC between
January 2013 to May 2016 were identified. Formalin-fixed paraffin embedded
tissue samples of these patients were analyzed for ALK gene rearrangement
using fluorescence in situ hybridization (FISH), utilizing break-apart probes
from Vysis (Abott Molecular, II, USA). Results: Eleven (11) cases exhibited ALK
gene rearrangement (6.4%). Nine out of eleven cases were stage IV and two
cases were stage III. Median patients age was 47 years (21-71 year) with male
predominance (males 77%, female 25%). All cases were moderately to poorly
differentiated adenocarcinoma. None of our cases showed signet ring cells or
abundant intracellular mucin. Conclusion: Our findings showed the incidence
of ALK gene rearrangement in lung adenocarcinoma in Saudi patients is 6.4%.
This is slightly higher in comparison to the published data which may be
attributed to KFSH&RC being a tertiary referral Center.
Keywords: lung adenocarcinoma, ALK rearrangement
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
MONDAY, DECEMBER 5, 2016
P1.02-005 FREQUENCY OF ACTIONABLE ALTERATIONS IN EGFR
WT NSCLC: EXPERIENCE OF THE WIDE CATCHMENT AREA OF
ROMAGNA (AVR)
Elisa Chiadini 1 , Angelo Delmonte 2 , Laura Capelli 1 , Nicoletta De Luigi 2 ,
Alessandro Gamboni 3 , Claudia Casanova 4 , Claudio Dazzi 4 , Maximilian Papi 5 ,
Sara Bravaccini 1 , Maria Maddalena Tumedei 1 , Alessandra Dubini 6 , Maurizio
Puccetti 7 , Lucio Crinò 8 , Paola Ulivi 1
1 Biosciences Laboratory, Istituto Scientifico Romagnolo Per Lo Studio E La Cura
Dei Tumori (IRST) IRCCS, Meldola/Italy, 2 Medical Oncology, Istituto Scientifico
Romagnolo Per Lo Studio E La Cura Dei Tumori (IRST) IRCCS, Meldola/Italy, 3 Medical
Oncology, Degli Infermi Hospital, Faenza/Italy, 4 Medical Oncology, S. Maria
Delle Croci Hospital, Ravenna/Italy, 5 Medical Oncology, Infermi Hospital, Rimini/
Italy, 6 Pathology Unit, Morgagni-Pierantoni Hospital, Forli/Italy, 7 Pathology, S.
Maria Delle Croci Hospital, Ravenna/Italy, 8 Medical Oncology, Santa Maria Della
Misericordia Hospital, Azienda Ospedaliera Di Perugia, Perugia/Italy
Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase
inhibitors have improved the outcome of patients with EGFR-mutated lung
adenocarcinoma (ADC). However, EGFR mutation occurred in about only
10-15% of ADC, but other alterations are emerging as potential target of
drugs. We analyzed the frequency of potentially targetable driver alterations
in a series of advanced EGFR-wild type (wt) NSCLC patients. Methods: 724
advanced EGFR-wt NSCLC patients enrolled from the Wide Catchment Area
of Romagna (AVR) between January 2013 to December 2014 were included
in the study. KRAS, BRAF, ERBB2, PIK3CA, NRAS, ALK, MAP2K1, RET and
DDR2 mutations were analyzed by Myriapod ® Lung Status kit (Diatech
Pharmacogenetics) on MassARRAY ® (SEQUENOM ® Inc, California). ERBB4 was
evaluated by direct sequencing and EML4-ALK and ROS1 rearrangements were
assessed by immunohistochemistry or fluorescence in situ hybridization.
Results: 331 (45.7%) patients showed at least one alteration. Of these, 72.2%,
6.3%, 3.6%, 1.8%, 2.1% and 1.2% patients had mutations in KRAS, BRAF,
PIK3CA, NRAS, ERBB2 and MAP2K1 genes, respectively. Only one patient
showed a mutation in ERBB4 gene. EML4-ALK and ROS1 rearrangements were
observed in 4.3% and 1.4% of all patients, respectively. The distribution of
mutations in relation to gender and smoking habits is reported in the Table.
Overlapping mutations were observed in 7 KRAS-mutated patients: 2 (28.6%)
patients were also mutated in PIK3CA, 4 (57.1%) showed also an EML4- ALK
translocation and one (14.3%) had a ROS1 rearrangement. One (0.3%) patient
showed both BRAF and PIK3CA alterations. Correlation analyses between the
different mutations and patient outcome are ongoing.
GENE
Mutated
Patients
N (%)
Gender
Female
(%)
Male
(%)
Smoking Habits*
Smoker
(%)
Never
Smoker
(%)
KRAS 239 (33) 93 (39) 146 (61) 115 (48.1) 9 (3.8)
BRAF 21 (3) 11 (52.4) 10 (47.6) 11 (52.4) 1 (4.8)
NRAS 6 (0.8) 4 (66.7) 2 (33.3) 4 (66.7) -
PIK3CA 12 (1.6) 4 (33.3) 8 (66.7) 5 (41.7) -
MAP2K1 4 (0.5) - 4 (100) 1 (25) -
ERBB2 7 (0.9) 5 (71.4) 2 (28.6) - 1 (14.3)
EML4-ALK 31 (4.3)
20
(64.5)
11 (35.5) 12 (38.7) 8 (25.8)
ROS1 10 (1.4) 7 (70) 3 (30) 3 (30) 5 (50)
*: some data are missing Conclusion: Driver mutations were detected in about
50% of EGFR wt lung ADC patients. Such alterations could represent potential
targets for therapy and could be evaluated in routine multiplexed testing to
obtain a wider tumor molecular characterization.
Keywords: driver alterations, EGFR wt, MassARRAY
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
MONDAY, DECEMBER 5, 2016
P1.02-006 INTERLABORATORY VARIATION IN MOLECULAR TESTING
(EGFR, KRAS AND ALK) IN STAGE IV NON-SQUAMOUS NON-SMALL
CELL LUNG CANCER IN THE NETHERLANDS IN 2013
Chantal Kuijpers 1 , Lucy Overbeek 2 , Sandra Rotteveel 3 , René Van Ommen 4 ,
Koos Koole 1 , Henk-Jan Van Slooten 5 , Michel Van Den Heuvel 6 , Ronald
Damhuis 7 , Stefan Willems 1
1 Pathology, University Medical Center Utrecht, Utrecht/Netherlands, 2 Foundation
Palga, Houten/Netherlands, 3 Roche, Woerden/Netherlands, 4 Pfizer, Capelle Aan
Den Ijssel/Netherlands, 5 Symbiant Pathology Expert Centre, Alkmaar/Netherlands,
6 Thoracic Oncology, Netherlands Cancer Institute - Antoni Van Leeuwenhoek
Hospital, Amsterdam/Netherlands, 7 Netherlands Comprehensive Cancer
Organisation (Iknl), Utrecht/Netherlands
Background: Adequate testing for molecular changes in non-small cell lung
cancer (NSCLC) is necessary to ensure the best possible treatment. However,
it is unknown how well molecular testing is performed in daily practice.
Therefore we aimed to assess the performance of testing for EGFR, KRAS
mutation and ALK translocation in metastatic NSCLC on a nationwide basis.
Methods: Using the Netherlands Cancer Registry, all stage IV non-squamous
NSCLC from 2013 were identified and matched to the Dutch Pathology
Registry (PALGA). Data on molecular testing for EGFR, KRAS and ALK were
extracted from excerpts of pathology reports. Proportions of tested and
positive cases were determined and interlaboratory variation was assessed.
Finally, degree of concordance between ALK immunohistochemistry (IHC)
and fluorescent in situ hybridization (FISH) results was evaluated. Results: In
total, 3393 stage IV non-squamous NSCLCs were identified, and 3183 (93.8%)
were matched to PALGA. Fifty-two tumors were excluded as pathology
S252 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017