Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
among 3,3% of patients.
Analysis of mutations in exon 2 KRAS gene detected 3 types of mutations:
p.G12D (1,03%), p.G12C (2,06%) и p.G13C (1,03%). The frequency of all
mutations was 4,1% in the total group of patients. The mutations were found
only in tumor tissues of men. 75% of mutations carriers are smokers. Analysis
of KRAS gene mutations in association with the development of a specific
histological type of lung cancer showed that mutations are more common in
patients with AC (5,9%) than in patients with SCC (2,2%). Conclusion: Thus,
in the researched group of patients mutations in the EGFR gene were found
only among non-smoking women with AC, mutations in the EGFR gene were
detected only among men independently of histological type of NSCLC.
Keywords: Epidermal growth factor receptor, mutations, non-small cell lung
cancer
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
MONDAY, DECEMBER 5, 2016
multiple biomarker analyses and tumor heterogeneity. Mutation detection in
circulating cell-free tumor DNA (ctDNA) can overcome these caveats and also
be used for tracking tumor dynamics. The aim of this study was to evaluate
KRAS mutation detection in plasma samples from LA. Methods: Plasma
samples from 35 patients with histologically confirmed KRAS mutant LA were
collected at initiation of chemotherapy. KRAS mutations were assessed using
digital PCR technology (QuantStudio3D Digital PCR System, Thermofisher
Scientific). Correlation between ctDNA and tumor biopsies in terms of
mutation detection was analysed. In 5 cases plasma samples were obtained
during the course of the disease to monitor clonal dynamics. Results: Most
cases were male (71%), with stage IV disease (83%), and showed KRAS
mutation on codon12 (94%). KRAS mutation was found in plasma samples in
28/35 cases, showing a concordance with the tumor of 80%. In patients whose
disease was limited to thorax (stages II, III, and IVa) KRAS mutation was
detected in 7/10 (70%) plasma samples. Plasma/tumor biopsy concordance in
cases with extra-thoracic metastases was 84% (21/25). The 4 false negative
cases had low burden of extra-thoracic disease, with bone (2 cases), brain (1
case), and abdominal lymph node (1 case) as the only metastatic location
outside the thorax. KRAS clonal dynamics in plasma showed a good
correlation with treatment responses in some cases (figure 1).
P1.02-038 OVER- EXPRESSION OF EPIDERMAL GROWTH FACTOR
RECEPTOR 1 (EGFR1) GENE IN SERUM OF ADENOCARCINOMA LUNG
AT A TERTIARY LEVEL CENTRE IN NORTH INDIA
Ashraf Ansari 1 , Anant Mohan 1 , Mirza Masroor 2 , Alpana Saxena 2 , Kalpana
Luthra 3 , Karan Madan 4 , Vijay Hadda 4 , G. Khilnani 5 , Randeep Guleria 4
1 Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences,
Delhi/India, 2 Biochemistry, Maulana Azad Medical College, New Delhi/India,
3 Biochemistry, All India Institute of Medical Sciences, New Delhi/India, 4 Pulmonary
Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi/
India, 5 Dept of Pulmonary Medicine and Sleep Disorders, All India Institute of
Medical Sciences, New Delhi/India
Background: Epidermal growth factor receptor (EGFR) is a cell surface protein
that binds to epidermal growth factor. Over expression of EGFR1 in tumor
tissue has been observed in upto 65% of advanced non small cell lung cancer,
and has shown promising prognostic potential. In this study, we compared the
EGFR1 gene expression in serum adenocarcinoma lung with healthy controls.
Methods: We analyzed 61 newly diagnosed patients of adenocarcinoma lung
and 50 healthy controls. RNA was isolated from blood serum of all subjects
and real time PCR (RT- PCR) was performed after complementary DNA (cDNA)
synthesis. The level of EGFR1 expression in serum was calculated by relative
quantification method and expressed as fold-increase compared to compared
with controls. Expression levels were also correlated with various clinicopathological
parameters. Results: Out of 61 patients, 42 were males. The
mean (SD) age of the entire group was 54.5 (11.5) years. Most of the patients
(79%) had stage IV disease. 23 (38%) patients were current/ ex- smokers, with
median pack years of 10 (range, 0.5- 100). Majority of patients had KPS of
90 (51%) and ECOG 1 (74%) respectively. Activating mutations in EGFR were
observed in the tissue of 14 (21.3%) of 61 patients; of these, 9 were exon- 19
deletions and 4 were exon- 21 point mutations. In the patients, a 19.66
mean- fold increase in serum EGFR gene expression was observed compared
to healthy controls. No significant association was found between EGFR
expression and other variables i.e., sex, age, smoking habit, performance
status, stage of disease and EGFR mutation status. Conclusion: Serum
EGFR1 gene was over expressed by >16 fold in advanced adenocarcinoma lung
compared to healthy controls. The association of EGFR expression with other
clinical disease characteristics needs further exploration.
Keywords: EGFR expression, RT-PCR, adenocarcinoma lung
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
MONDAY, DECEMBER 5, 2016
P1.02-039 ASSESSMENT OF KRASMUTATIONS (BY DIGITAL PCR)
IN CIRCULATING TUMORAL DNA FROM LUNG ADENOCARCINOMA
PATIENTS
Álvaro Taus 1 , Laura Camacho 2 , Ainhoa Hernández 1 , Gabriel Piquer 2 , Eva
López 1 , Alba Dalmases 3 , David Casadevall 1 , Lara Pijuan 3 , Max Hardy 1 , Raquel
Longarón 3 , Pedro Rocha 1 , Arnau Zafra 2 , Joan Albanell 1 , Beatriz Bellosillo 3 ,
Edurne Arriola 1
1 Medical Oncology Department, Hospital Del Mar, Barcelona/Spain, 2 Imim (Institut
Hospital Del Mar D’Investigacions Mèdiques), Barcelona/Spain, 3 Pathology
Department, Hospital Del Mar, Barcelona/Spain
Background: KRAS mutations are detected in approximately 25% of lung
adenocarcinomas (LA). Targeted therapies against KRAS are under
investigation. The use of tumor biopsy for molecular testing may be
challenging due to the invasiveness of the procedure, the limited material for
Conclusion: High concordance in the detection of KRAS mutations was found
between plasma and tumor tissue using digital PCR technology, particularly in
cases with extra-thoracic disease. Digital PCR allows for tracking clonal
dynamics in KRAS mutant LA.
Keywords: liquid biopsy, KRAS, Clonal dynamics, lung adenocarcinoma
POSTER SESSION 1 - P1.02: BIOLOGY/PATHOLOGY
DRIVER GENES IN NSCLC, RESISTANCE, AND OTHER –
MONDAY, DECEMBER 5, 2016
P1.02-040 HETEROGENEITY OF THE EGFR / KRAS GENE MUTATION
IN MULTIFOCAL LUNG ADENOCARCINOMA AND THE CLINICAL
SIGNIFICANCE
Lin Li 1 , Susu Zhang 2 , Hongshuang Dai 2 , Jianming Ying 1 , Yanning Gao 2
1 Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences,
Beijing/China, 2 State Key Laboratory of Molecular Oncology, Cancer Hospital,
Chinese Academy of Medical Sciences, Beijing/China
Background: Significant advances on EGFR-targeted therapy have allowed
increasing availability of therapeutic options for non small cell lung
cancers. For multifocal lung adenocarcinoma patients in clinic, the EGFR
gene mutation is generally examined only on the largest tumor or the one
containing the most tumor cells, which could omit the tumors harboring the
EGFR mutation and thus loss of opportunity for the tyrosine kinase inhibitors
therapy. Methods: A total of 58 cases of multifocal lung adenocarcinoma,
including 129 intrapulmonary tumors resected surgically, was recruited for
this study. The genome DNA samples were prepared from formalin-fixed and
paraffin-embedded tumor tissues. The EGFR / KRAS mutational status of
each tumor was examined by Sanger’s DNA sequencing. The targeted hotspot
mutations in EGFR gene included p.G719S/C/A (exon 18), p.T790M (exon 20),
p.S768I (exon 20), p.L858R (exon 21), p.L861Q (exon 21) and deletions in exon
19. The hotspot mutations in KRAS gene were within codon 12 including
p.G12C/V/S/R/D/A. Results: In this group of 58 patients with multifocal
lung adenocarcinoma, 38 patients were found EGFR or KRAS mutations
in their tumors. Among them, the EGFR mutations were detected in 59
tumors derived from 34 cases; while the KRAS mutations were detected in
7 tumors from 5 cases. One patient (Case 30) was identified EGFR (exon 18,
p.G719A) or KRAS (p.G12A or p.G12C) mutation in her 3 tumors, respectively.
Copyright © 2016 by the International Association for the Study of Lung Cancer
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