Table 1– Comparison of intra-tumoural heterogeneity of EGFR mutational status in resected primary tumour with trans-sectional analysis

First author, year [ref.]	Population studied	Cases/sections or areas per case n/N	Detection methods	Tumour enrichment strategy	*Pure mutated EGFR* cases (group A)**	*Pure wild-type EGFR* cases (group B)**	EGFR mutant with heterogeneity (group C)	PFS response to EGFR-TKIs
Yatabe, 2011 [22]	Resected lung adenocarcinoma with EGFR mutation	50/3 5/>100	Cycleave PCR/FA	Manual MD	100	NA	0	NA
Sun, 2012 [23]	Early-stage mixed adenocarcinoma	10/2–3	DS	Manual MD	80	20	0	NA
Mattsson, 2012 [24]	Resected NSCLC with EGFR mutation	6/3	DS	Manual MD	100	NA	0	NA
Jiang, 2008 [17]	Stage IIIB/IV EGFR mutated gefitinib-responsive NSCLC with AR	6/11–32	DS	Laser MD	50	NA	50	NA
Taniguchi, 2008 [18]	Resected NSCLC treated with gefitinib for postoperative recurrence	21/50–60	SNaP shot	Laser MD	71.4	NA	28.6	18 months for group A versus 7.5 months for group C
Bai (2012) [19]	Stage III/IV NSCLC with palliative resection	79/30–40	DHPLC/ARMS	Laser MD	20.3	41.8	38	NA
Bai, 2013 [20]	Stage III/IV NSCLC with palliative resection	85/total 2699 areas	DHPLC/ARMS	Laser MD	24.7 (DHPLC) 36.5 (ARMS)	42.4 (DHPLC) 35.3 (ARMS)	32.9 (DHPLC) 28.2 (ARMS)	16 months for group A versus 11 months for group C versus 3 months for group B
Tomonaga, 2013 [21]	Stage I resected mixed adenocarcinoma	38/NA	RFLP	Laser MD	26.3	50	24	NA

Data are presented as %, unless otherwise stated. EGFR: epidermal growth factor receptor; PFS: progression-free survival; TKI: tyrosine kinase inhibitor; FA: fragment analysis; MD: microdissection; NA: not available; DS: direct Sanger sequencing; NSCLC: nonsmall cell lung cancer; AR: acquired resistance; SNaP shot: single nucleotide primer extension reaction using the SNaPshot multiplex kit (Life Technologies, Carlsbad, CA, USA); DHPLC: denaturing high-performance liquid chromatography; ARMS: amplification refractory mutation system; RFLP: restriction fragment length polymorphism.