World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Original Article

Volume 10, Number 3, June 2019, pages 142-150

Epidermal Growth Factor Receptor Mutation Frequency in Squamous Cell Carcinoma and Its Diagnostic Performance in Cytological Samples: A Molecular and Immunohistochemical Study

**Table 1.** EGFR Genotype With Clinicopathological Parameters
Features	EGFR mutant (n = 79)	EGFR wild (n = 171)	P value
Age
≤ 40 years (n = 17)	8 (47.0%)	9 (53%)	0.1
> 40 years (n = 233)	71 (30.5%)	162 (59.5%)	0.1
Gender
Men (n = 175)	49 (28%)	126 (72%)	0.06
Women (n = 75)	30 (40%)	45 (60%)	0.06
Smoking
Present (n = 115)	29 (36.8%)	86 (50.3%)	0.05
Absent (n = 135)	50 (63.2%)	85 (49.7%)	0.05
Pleural effusion
Present (n = 99)	38 (38.4%)	61 (61.6%)	0.06
Absent (n = 151)	41 (27.2%)	110 (72.8%)	0.06
Malignant effusion
Present (n = 45)	19 (42.2%)	26 (57.8%)	0.1
Absent (n = 12)	2 (16.7%)	10 (83.3%)	0.1
Histology
Adenocarcinoma	69 (36.5%)	120 (63.5%)	0.02
Squamous cell carcinoma	7 (15%)	39 (85%)	0.02
NSCLC-NOS	3 (27.3%)	8 (72.7%)	0.02
Adenosquamous carcinoma	0	4 (100%)	0.02

Table 1. EGFR Genotype With Clinicopathological Parameters

Features

EGFR mutant (n = 79)

EGFR wild (n = 171)

P value

Age

≤ 40 years (n = 17)

8 (47.0%)

9 (53%)

0.1

> 40 years (n = 233)

71 (30.5%)

162 (59.5%)

0.1

Gender

Men (n = 175)

49 (28%)

126 (72%)

0.06

Women (n = 75)

30 (40%)

45 (60%)

0.06

Smoking

Present (n = 115)

29 (36.8%)

86 (50.3%)

0.05

Absent (n = 135)

50 (63.2%)

85 (49.7%)

0.05

Pleural effusion

Present (n = 99)

38 (38.4%)

61 (61.6%)

0.06

Absent (n = 151)

41 (27.2%)

110 (72.8%)

0.06

Malignant effusion

Present (n = 45)

19 (42.2%)

26 (57.8%)

0.1

Absent (n = 12)

2 (16.7%)

10 (83.3%)

0.1

Histology

Adenocarcinoma

69 (36.5%)

120 (63.5%)

0.02

Squamous cell carcinoma

7 (15%)

39 (85%)

0.02

NSCLC-NOS

3 (27.3%)

8 (72.7%)

0.02

Adenosquamous carcinoma

4 (100%)

0.02

**Table 2.** Comparison Between EGFR Mutation by Real-Time PCR and Immunohistochemistry
Real-time PCR (n = 112)	Mutation-specific antibody immunohistochemistry
^aTwo cases of L858R were positive for both mutation-specific antibodies; ^bOne case of DEL19 was positive for both mutation-specific antibodies; ^cOne case of wild type was positive for both mutation-specific antibodies.
L858R (n = 20)	11^a	02^a	09
DEL19 (n = 9)	01^b	03^b	06
G719X (n = 3)	00	01	02
T790M (n = 2)	01	00	01
INS (n = 1)	00	00	01
Wild (n = 76)	06^c	04^c	68

Table 2. Comparison Between EGFR Mutation by Real-Time PCR and Immunohistochemistry

Real-time PCR (n = 112)

Mutation-specific antibody immunohistochemistry

L858R (n = 19) (43B2)

DEL19 (n = 10) (6B6)

Wild (n = 87)

^aTwo cases of L858R were positive for both mutation-specific antibodies; ^bOne case of DEL19 was positive for both mutation-specific antibodies; ^cOne case of wild type was positive for both mutation-specific antibodies.

L858R (n = 20)

11^a

02^a

DEL19 (n = 9)

01^b

03^b

G719X (n = 3)

T790M (n = 2)

INS (n = 1)

Wild (n = 76)

06^c

04^c

**Table 3.** Sensitivity and Specificity of Mutation-Specific EGFR Antibodies
Mutation-specific antibodies	True positive	True negative	False positive	False negative	Sensitivity (%)	Specificity (%)
L858R (n = 112)	11	84	08	09	55	91.3
DEL (n = 112)	03	96	07	06	33.3	93.2
Total	14	180	15	15	48.3	92.3

Table 3. Sensitivity and Specificity of Mutation-Specific EGFR Antibodies

Mutation-specific antibodies

True positive

True negative

False positive

False negative

Sensitivity (%)

Specificity (%)

L858R (n = 112)

91.3

DEL (n = 112)

33.3

93.2

Total

180

48.3

92.3

**Table 4.** Comparison of EGFR Mutation Between Biopsy and Malignant Effusion Specimen
Biopsy specimen (n = 20)	Malignant effusion specimen (n = 20)
L858R	5	-	-	-	-	-	1
DEL19	-	3	-	-	-	-	-
T790M	-	-	-	-	-	-	-
G719A	-	-	-	-	-	-	-
INS	-	-	-	-	-	-	-
Wild	1		-	2	-	7	-
Unsuccessful	-	-	-	-	-	1	-

Table 4. Comparison of EGFR Mutation Between Biopsy and Malignant Effusion Specimen

Biopsy specimen (n = 20)

Malignant effusion specimen (n = 20)

L858R

DEL19

T790M

G719A

INS

Wild

Unsuccessful

L858R

DEL19

T790M

G719A

INS

Wild

Unsuccessful

**Table 5.** Frequency Distribution of EGFR Mutation in Non-Small Cell Lung Cancer
Area	Authors	Country	Year	EGFR mutation (%)
Europe	Leduc et al [32]	France	2017	37
Isaksson et al [27]	Sweeden	2013	11
Sarosi et al [33]	Hungary	2016	9.8
De Greve et al [34]	Belgium	2016	27
Gervas et al [31]	Serbia	2015	19
Chatziandreou et al [4]	Greece	2015	10.6
Schmid-Bindert et al [35]	Germany	2013	40.8
Schmid et al [36]	Austria	2009	7.3
Arrieta et al [37]	Mexico	2015	27.0
Martin et al [38]	Canada	2016	29.7
Lopez-Chavez et al [39]	USA	2016	21.9
South America	de Castro et al [29]	Brazil	2017	17
Arrieta et al [30]	Argentina	2011	18
Asia-Pacific	Zhou et al [19]	China	2017	34.9
Yotsukura et al [17]	Japan	2017	46.9
Rahman et al [18]	Japan	2014	22.9
Kim et al [8]	Korea	2015	40.3
Toh et al [20]	Singapore	2010	39
Chang et al [21]	Taiwan	2007	76.5
Shi et al [22]	Vietnam	2014	64
Australia	Cooper et al [23]	Australia	2013	14.7
Sriram et al [40]	Australia	2011	7.1
India	Kasana et al [26]	India	2016	35.1
Maturu et al [25]	India	2016	16.6
Doval et al [24]	India	2013	25.9

Table 5. Frequency Distribution of EGFR Mutation in Non-Small Cell Lung Cancer

Area

Authors

Country

Year

EGFR mutation (%)

Europe

Leduc et al [32]

France

2017

Isaksson et al [27]

Sweeden

2013

Sarosi et al [33]

Hungary

2016

9.8

De Greve et al [34]

Belgium

2016

Gervas et al [31]

Serbia

2015

Chatziandreou et al [4]

Greece

2015

10.6

Schmid-Bindert et al [35]

Germany

2013

40.8

Schmid et al [36]

Austria

2009

7.3

Arrieta et al [37]

Mexico

2015

27.0

Martin et al [38]

Canada

2016

29.7

Lopez-Chavez et al [39]

USA

2016

21.9

South America

de Castro et al [29]

Brazil

2017

Arrieta et al [30]

Argentina

2011

Asia-Pacific

Zhou et al [19]

China

2017

34.9

Yotsukura et al [17]

Japan

2017

46.9

Rahman et al [18]

Japan

2014

22.9

Kim et al [8]

Korea

2015

40.3

Toh et al [20]

Singapore

2010

Chang et al [21]

Taiwan

2007

76.5

Shi et al [22]

Vietnam

2014

Australia

Cooper et al [23]

Australia

2013

14.7

Sriram et al [40]

Australia

2011

7.1

India

Kasana et al [26]

India

2016

35.1

Maturu et al [25]

India

2016

16.6

Doval et al [24]

India

2013

25.9

**Table 6.** Sensitivity and Specificity of Mutation-Specific EGFR IHC With Molecular Testing
Author	Country	Year	Sensitivity (DEL19 + L858R)	Specificity (DEL19 + L858R)
Brevet et al [9]	USA	2010	84	98.9
Kitamura et al [47]	Japan	2010	47	96
Seo et al [10]	Korea	2014	76.6	89
Kim et al [8]	Korea	2015	75.6	94.5
Zhang et al [46]	China	2016	83.7	98.6

Table 6. Sensitivity and Specificity of Mutation-Specific EGFR IHC With Molecular Testing

Author

Country

Year

Sensitivity (DEL19 + L858R)

Specificity (DEL19 + L858R)

Brevet et al [9]

USA

2010

98.9

Kitamura et al [47]

Japan

2010

Seo et al [10]

Korea

2014

76.6

Kim et al [8]

Korea

2015

75.6

94.5

Zhang et al [46]

China

2016

83.7

98.6