Introduction
Patients and methods
Patients
Gender | |
---|---|
Male | 13 |
Female | 27 |
Age
(years)
| Mean 64 [42 – 81] |
Tobacco status
| |
≤ 10 Pack per year | 15 |
> 10 Pack per year | 14 |
unknown | 11 |
TNM stage at initial diagnosis* | |
I | 4 |
II | 4 |
III | 9 |
IV | 20 |
Unknown | 3 |
Samples
Number and type of samples analyzed per patients | EGFR genotyping results | ||||||||
---|---|---|---|---|---|---|---|---|---|
Patients | Mutation type | Primary tumor(sugical sample,lung biopsy*,bronchial biospy£) | PLEURAL BIOPSY | LYMPH NODE | Cytology: Pleural Effusion,Bronchial aspiration* | Contributive samples | Concordant EGFR status | Non contributive samples | Discordant EGFR status |
P1 | del19 | 7 | 0 | 0 | 0 | 7 | 7 | 0 | |
P2 | del19 | 2 | 0 | 0 | 0 | 2 | 2 | 0 | |
P3 | del19 | 0 | 3 | 0 |
1
| 4 | 3 | 0 |
1 (rescued by CAST PCR)
|
P4 | del19 | 0 | 4 | 0 | 1 | 5 | 5 | 0 | |
P5 | del19 | 0 | 3 | 0 | 1 | 4 | 4 | 0 | |
P6 | del19 | 1* + 1* | 0 | 0 | 0 | 2 | 2 | 0 | |
P7 | del19 | 0 | 0 | 0 | 2 | 2 | 2 | 0 | |
P8 | del19 | 1* + 1* | 0 | 0 | 0 | 2 | 2 | 0 | |
P9 | del19 | 3 | 1 | 0 | 0 | 4 | 4 | 0 | |
P10 | del19 | 0 | 3 | 0 | 0 | 3 | 3 | 0 | |
P11 | del19 | 0 | 3 | 0 | 0 | 3 | 3 | 0 | |
P12 | del19 | 0 | 3 | 0 | 0 | 2 | 2 | 1 | |
P13 | del19 | 4 | 0 | 0 | 0 | 4 | 4 | 0 | |
P14 | del19 | 2 | 0 | 0 | 0 | 2 | 2 | 0 | |
P15 | del19 | 0 | 2 | 0 | 1 | 3 | 3 | 0 | |
P16 | del19 | 1£ + 1£
| 0 | 0 |
1*
| 3 | 1 | 0 |
2 (remained WT by CAST PCR)
|
P17 | del19 | 3 | 0 | 0 | 0 | 3 | 3 | 0 | |
P18 | del19 | 0 | 0 | 1 | 1* | 1 | 1 | 1 | |
P19 | del19 | 1 + 1* | 0 | 0 | 0 | 2 | 2 | 0 | |
P20 | p.G719A | 1 | 0 | 4 | 0 | 5 | 5 | 0 | |
P21 | p.G719A | 5 | 0 | 2 | 0 | 7 | 7 | 0 | |
P22 | ins20 | 3 | 0 | 1 | 0 | 4 | 4 | 0 | |
P23 | ins20 | 0 | 2 | 0 | 0 | 2 | 2 | 0 | |
P24 | ins20 | 3 | 0 | 2 | 0 | 4 | 4 | 1 | |
P25 | ins20 | 0 | 2 | 0 | 0 | 2 | 2 | 0 | |
P26 | ins20 | 3 | 0 | 0 | 0 | 3 | 3 | 0 | |
P27 | ins20 | 2 + 1
| 0 | 1 + 1
| 0 | 4 | 2 | 1 | 2 |
P28 | p.L858R | 4 | 0 | 2 | 0 | 6 | 6 | 0 | |
P29 | p.L858R | 1£ + 1£ | 0 | 0 | 0 | 2 | 2 | 0 | |
P30 | p.L858R | 2 | 0 | 0 | 0 | 2 | 2 | 0 | |
P31 | p.L858R | 3 | 0 | 0 | 0 | 3 | 3 | 0 | |
P32 | p.L858R | 0 | 3 | 0 | 1 | 4 | 4 | 0 | |
P33 | p.L858R | 0 | 3 | 0 | 0 | 3 | 3 | 0 | |
P34 | p.L858R | 1£ | 1 | 0 | 1 | 3 | 3 | 0 | |
P35 | p.L858R | 4 | 0 | 2 | 0 | 6 | 6 | 0 | |
P36 | p.L858R | 2 | 0 | 1 | 0 | 3 | 3 | 0 | |
P37 | p.L858R | 3 | 0 | 0 | 0 | 3 | 3 | 0 | |
P38 | p.L858R | 3 | 0 | 0 | 0 | 3 | 3 | 0 | |
P39 | p.L858R | 3 | 0 | 0 | 0 | 3 | 3 | 0 | |
P40 | p.L861Q/p.T790M | 19 | 0 | 0 | 0 | 19 | 19 | 0 |
Molecular analysis
EGFR copy number
Results
Number and type of samples analyzed per patients |
EGFR CNV results | |||||||
---|---|---|---|---|---|---|---|---|
Patients | Mutation type | Primary tumor(sugical sample,lung biopsy*, bronchial biospy£ | Pleural biopsy | Lymph node | Cytology: Pleural effusion,Bronchial Aspiration* | EGFR CNV ≥ 2.5 | EGFR CNV < 2.5 | Non contributive samples |
P1
|
del19
| 7 | 0 | 0 | 0 | 5 | 2 | |
P2
|
del19
| 2 | 0 | 0 | 0 | 2 | ||
P3
|
del19
| 0 | 3 | 0 | 1 | 3 | 1 | |
P4
|
del19
| 0 | 4 | 0 | 1 | 1 | 3 | 1 |
P5
|
del19
| 0 | 3 | 0 | 1 | 1 | 3 | |
P6
|
del19
| 1* + 1* | 0 | 0 | 0 | 1 | 1 | |
P7
|
del19
| 0 | 0 | 0 | 2 | 1 | 1 | |
P8
|
del19
| 1* + 1* | 0 | 0 | 0 | 1 | 1 | |
P9
|
del19
| 3 | 1 | 0 | 0 | 1 | 3 | |
P10
|
del19
| 0 | 3 | 0 | 0 | 1 | 2 | |
P11
|
del19
| 0 | 3 | 0 | 0 | 3 | ||
P12
|
del19
| 0 | 3 | 0 | 0 | 1 | 2 | |
P13
|
del19
| 4 | 0 | 0 | 0 | 4 | ||
P14
|
del19
| 2 | 0 | 0 | 0 | 2 | ||
P15
|
del19
| 0 | 2 | 0 | 1 | 3 | ||
P16
|
del19
| 1£ + 1£ | 0 | 0 | 1* | 1 | 2 | |
P17
|
del19
| 3 | 0 | 0 | 0 | 1 | 1 | 1 |
P18
|
del19
| 0 | 0 | 1 | 1* | 1 | 1 | |
P19
|
del19
| 1 + 1* | 0 | 0 | 0 | 1 | 1 | |
P20
|
p.G719A
| 1 | 0 | 4 | 0 | 1 | 2 | 2 |
P21
|
p.G719A
| 5 | 0 | 2 | 0 | 6 | 1 | |
P22
|
ins20
| 3 | 0 | 1 | 0 | 2 | 2 | |
P23
|
ins20
| 0 | 2 | 0 | 0 | 2 | ||
P24
|
ins20
| 3 | 0 | 2 | 0 | 4 | 1 | |
P25
|
ins20
| 0 | 2 | 0 | 0 | 1 | 1 | |
P26
|
ins20
| 3 | 0 | 0 | 0 | 3 | ||
P27
|
ins20
| 2 + 1 | 0 | 1 + 1 | 0 | 4 | 1 | |
P28
|
p.L858R
| 4 | 0 | 2 | 0 | 6 | ||
P29
|
p.L858R
| 1£ + 1£ | 0 | 0 | 0 | 1 | 1 | |
P30
|
p.L858R
| 2 | 0 | 0 | 0 | 2 | ||
P31
|
p.L858R
| 3 | 0 | 0 | 0 | 3 | ||
P32
|
p.L858R
| 0 | 3 | 0 | 1 | 2 | 2 | |
P33
|
p.L858R
| 0 | 3 | 0 | 0 | 1 | 1 | 1 |
P34
|
p.L858R
| 1£ | 1 | 0 | 1 | 1 | 2 | |
P35
|
p.L858R
| 4 | 0 | 2 | 0 | 6 | ||
P36
|
p.L858R
| 2 | 0 | 1 | 0 | 2 | 1 | |
P37
|
p.L858R
| 3 | 0 | 0 | 0 | 2 | 1 | |
P38
|
p.L858R
| 3 | 0 | 0 | 0 | 1 | 2 | |
P39
|
p.L858R
| 3 | 0 | 0 | 0 | 2 | 1 | |
P40
|
p.L861Q/
p.T790M
| 19 | 0 | 0 | 0 | 18 | 1 |
Discussion
Article | Histological subtype | No of samples | Smoking status | Concordance PT/M | Analysis within PT | Concordance within PT | Method | Mutation type | Metastatic sites |
---|---|---|---|---|---|---|---|---|---|
Yatabe et al. 2011[17] | ADC (77) | 77 | 100 | qPCR | L858R | Lymph nodes | |||
Fragment analysis | DEL19 | ||||||||
INS20 | |||||||||
719X | |||||||||
Sun et al. 2011[37] | ADC (39), SCC (31), ADSQ (6), LCC (4) | 80 | Ever (49) | Direct sequencing | all | Lymph nodes | |||
Never (31) | |||||||||
Global | 92,5% (74/80) | ||||||||
Wei et al. 2014[41] | ADC (49) | 50 | Ever (10) | 80% | qPCR (commercial kit) | 45 hotspots | Lymph nodes | ||
SCC (1) | |||||||||
Never (40) | 97,5% | ||||||||
Global | 93% (47/50) | ||||||||
Bai et al. 2013[36] | ADC (63) | 85 (45 EGFRmt 40 EGFRwt) | 1431 foci | 87,1% | ARMS | DXS EGFR mutation Kit | |||
SCC (10) | 1238 foci (foci : capture with laser microdissection 0,1cm2) | 4 cases with 5% - 8% of foci showing mutations | |||||||
ADSQ (5) | |||||||||
Other (7) | |||||||||
Chang et al. 2011[42] | ADC (34) | 56 (27 EGFRmt) | Ever (29) | 62% | Direct sequencing | all | Lymph nodes | ||
SCC (17) | |||||||||
ADSQ (1) | Never (23) | 70% | |||||||
Other (1) | Unknown (4) | ||||||||
Global | 68% (38/56) | ||||||||
Schmid et al. 2009[33] | ADC (96) | 96 (7 EGFRmt) | Ever (74) | Direct sequencing | L858R (3) | Lymph nodes | |||
DEL19 (3) | |||||||||
Never (22) | INS20 (1) | ||||||||
Global | 14% (1/7) | ||||||||
Gow et al 2009[34] | ADC (42) | 67 (35 EGFRmt) | Ever (26) | Direct sequencing and ARMS for discordant results | all | Brain (25) | |||
SCC (21) | Bone (20) | ||||||||
ADSQ (0) | (19 with adjuvant treatment before molecular analysis on metastatic site) | Never (41) | Other (22) | ||||||
Other (4) | Global | 26% (9/35) seq and 57 %(20/35) ARMS | |||||||
Mattsson et al. 2012[18] | ADC (6) | 6 | 3 foci per tumor (distinct morphologies) | 100% | Direct sequencing | L858R and DEL19 | |||
Kalikaki et al. 2008[35] | ADC (20) | 25 (7 EGFRmt) | Ever (22) | Direct sequencing | all | Brain (3) | |||
SCC (2) | Pleura (5) | ||||||||
ADSQ (0) | (17 with adjuvant treatment before molecular analysis on metastatic site) | Never (3) | Lung (9) | ||||||
Other (3) | Global | 14% (1/7) 5 mutations are rare alterations (codons 692-847-746-857) | Adrenal gland (3) | ||||||
Bone (2) | |||||||||
Skin (1) | |||||||||
Liver (1) | |||||||||
Matsumoto et al. 2006[43] | ADC (19) | 19 (12 EGFRmut) | 100% | Direct sequencing | L858R, DEL19 | Brain (19) | |||
Yatabe et al. 2011[17] | ADC (50) | 50 EGFRmt | 3 foci per tumor (50) | 100% | qPCR | L858R | |||
Fragment analysis | DEL19 | ||||||||
100 foci per tumor (5) | 100% |