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 6, Number 3, June 2015, pages 355-363

Does Immunohistochemistry for Discovered on GIST1 and Minichromosome Maintenance Protein7 Provide Additional Clinicopathological Value in Gastrointestinal Stromal Tumors?

Figure 1. Representative sections of gastrointestinal stromal tumors with positive DOG1 immunostaining: score 2+ (a) and score 4 (b), and positive C-KIT immunostaining: score 2+ (c) and score 4+ (d). A case of epithelioid GIST with positive DOG1 expression and negative C-KIT (e, f). A case of poorly differentiated carcinoma positive for DOG1 expression (g) and a case of leimyosarcoma positive for C-KIT expression (h). Immunohistochemistry, 3,3' diaminobenzidine chromogen and hematoxylin counterstaining. Original magnification × 200 and × 400.

Figure 2. Representative sections of gastrointestinal stromal tumors with positive MCM7 (a) and Ki-67 (b) expression with high and low LIs respectively. Immunohistochemistry, 3,3' diaminobenzidine chromogen and hematoxylin counterstaining. Original magnification × 400. Significant positive correlation between MCM7 and Ki-67 labeling indices (LIs) in gastrointestinal stromal tumors (c).

**Table 1.** Clinicopathological Characteristics of 43 GISTs
Clinicopathological characteristics	n (%)
Gender
Male	24 (55.8%)
Female	19 (44.2%)
Tumor location
Gastric	28 (65.1%)
Small intestine	14 (32.6%)
Colon	1 (2.3%)
Tumor type
Spindle	34 (79%)
Epithelioid	6 (14%
Mixed	3 (7%)
Tumor size
≤ 5 cm	3 (7%)
> 5 - 10 cm	11 (25.6%)
> 10 cm	29 (67.4%)
Tumor mitotic rate
≤ 5/50 HPF	24 (55.8%)
> 5/50 HPF	19 (44.2%)
Risk
Low	9 (20.9%)
Intermediate	11 (25.6%)
High	23 (53.5%)

Table 1. Clinicopathological Characteristics of 43 GISTs

Clinicopathological characteristics

n (%)

Gender

Male

24 (55.8%)

Female

19 (44.2%)

Tumor location

Gastric

28 (65.1%)

Small intestine

14 (32.6%)

Colon

1 (2.3%)

Tumor type

Spindle

34 (79%)

Epithelioid

6 (14%

Mixed

3 (7%)

Tumor size

≤ 5 cm

3 (7%)

> 5 - 10 cm

11 (25.6%)

> 10 cm

29 (67.4%)

Tumor mitotic rate

≤ 5/50 HPF

24 (55.8%)

> 5/50 HPF

19 (44.2%)

Risk

Low

9 (20.9%)

Intermediate

11 (25.6%)

High

23 (53.5%)

**Table 2.** Diagnostic Efficacy of DOG1 and C-KIT in GISTs
	TP	FN	TN	FP	Sensitivity	Specificity	PPV	NPV	Accuracy
TN: true negative; TP: true positive; FN: false negative; FP: false positive; PPV: positive predictive value; NPV: negative predictive value.
DOG1	42	1	29	1	97.67%	96.67%	97.67%	96.67%	97.26%
KIT	39	4	25	5	90.70%	83.33%	88.64%	86.21%	87.67%

Table 2. Diagnostic Efficacy of DOG1 and C-KIT in GISTs

Sensitivity

Specificity

PPV

NPV

Accuracy

TN: true negative; TP: true positive; FN: false negative; FP: false positive; PPV: positive predictive value; NPV: negative predictive value.

DOG1

97.67%

96.67%

97.67%

96.67%

97.26%

KIT

90.70%

83.33%

88.64%

86.21%

87.67%

**Table 3.** Associations of DOG1 and C-KIT With Clinicopathological Characteristics
Variables	n	DOG1 expression score	C-KIT expression score
SI: small intestine. Tests of significance: Chi-square test and Fisher’s exact tests. P-value ≤ 0.05 is considered significant.
Age				0.359			0.219
< 57 years	20	7 (35.0%)	13 (65.0%)		11 (55.0%)	9 (45.0%)
≥ 57 years	23	12 (52.2%)	11 (47.8%)		17 (73.9%)	6 (26.1%)
Gender				1.000			0.521
Male	24	11 (45.8%)	13 (54.2%)		17 (70.8%)	7 (29.2%)
Female	19	8 (42.1%)	11 (57.9%)		11 (57.9%)	8 (42.1%)
Tumor location				0.453			0.375
Gastric	28	14 (50%)	14 (50%)		19 (67.9%)	9 (32.1%)
SI	14	5 (35.7%)	9 (64.3%)		9 (64.3%)	5 (35.7%)
Colon	1	-	1 (100%)		-	1 (100%)
Tumor type				0.473			0.215
Spindle	34	14 (41.2%)	20 (58.8%)		20 (58.8%)	14 (41.2%)
Epithelioid	6	4 (66.7%)	2 (33.3%)		5 (83.3%)	1 (16.7%)
Mixed	3	1 (33.3%)	2 (66.7%)		3 (100%)	-
Tumor size				0.023			0.121
≤ 5 cm	3	3 (100%)	-		3 (100%)	-
> 5 - 10 cm	11	7 (63.6%)	4 (36.4%)		9 (81.8%)	2 (18.2%)
> 10 cm	29	9 (31.0%)	20 (69.0%)		16 (55.2%)	13 (44.8%)
Tumor mitotic rate				0.217			0.521
≤ 5/50 HPF	24	13 (54.2%)	11 (45.8%)		17 (70.8%)	7 (29.2%)
> 5/50 HPF	19	6 (31.6%)	13 (68.4%)		11 (57.9%)	8 (42.1%)
Risk				0.037			0.121
Low	9	6 (66.7%)	3 (33.3%)		8 (88.9%)	1 (11.1%)
Intermediate	11	7 (63.6%)	4 (36.4%)		8 (72.7%)	3 (27.3%)
High	23	6 (26.1%)	17 (73.9%)		12 (52.2%)	11 (47.8%)
Metastasis				1.000			0.692
Yes	8	4 (50%)	4 (50%)		6 (75.0%)	2 (25.0%)
No	35	15 (42.9%)	20 (57.1%)		22 (62.9%)	13 (37.1%)

Table 3. Associations of DOG1 and C-KIT With Clinicopathological Characteristics

Variables

DOG1 expression score

C-KIT expression score

Score 0, 1, 2

Score 3, 4

P-value

Score 0, 1, 2

Score 3, 4

P-value

SI: small intestine. Tests of significance: Chi-square test and Fisher’s exact tests. P-value ≤ 0.05 is considered significant.

Age

0.359

0.219

< 57 years

7 (35.0%)

13 (65.0%)

11 (55.0%)

9 (45.0%)

≥ 57 years

12 (52.2%)

11 (47.8%)

17 (73.9%)

6 (26.1%)

Gender

1.000

0.521

Male

11 (45.8%)

13 (54.2%)

17 (70.8%)

7 (29.2%)

Female

8 (42.1%)

11 (57.9%)

8 (42.1%)

Tumor location

0.453

0.375

Gastric

14 (50%)

19 (67.9%)

9 (32.1%)

5 (35.7%)

9 (64.3%)

5 (35.7%)

Colon

1 (100%)

Tumor type

0.473

0.215

Spindle

14 (41.2%)

20 (58.8%)

14 (41.2%)

Epithelioid

4 (66.7%)

2 (33.3%)

5 (83.3%)

1 (16.7%)

Mixed

1 (33.3%)

2 (66.7%)

3 (100%)

Tumor size

0.023

0.121

≤ 5 cm

3 (100%)

> 5 - 10 cm

7 (63.6%)

4 (36.4%)

9 (81.8%)

2 (18.2%)

> 10 cm

9 (31.0%)

20 (69.0%)

16 (55.2%)

13 (44.8%)

Tumor mitotic rate

0.217

0.521

≤ 5/50 HPF

13 (54.2%)

11 (45.8%)

17 (70.8%)

7 (29.2%)

> 5/50 HPF

6 (31.6%)

13 (68.4%)

11 (57.9%)

8 (42.1%)

Risk

0.037

0.121

Low

6 (66.7%)

3 (33.3%)

8 (88.9%)

1 (11.1%)

Intermediate

7 (63.6%)

4 (36.4%)

8 (72.7%)

3 (27.3%)

High

6 (26.1%)

17 (73.9%)

12 (52.2%)

11 (47.8%)

Metastasis

1.000

0.692

Yes

4 (50%)

6 (75.0%)

2 (25.0%)

15 (42.9%)

20 (57.1%)

22 (62.9%)

13 (37.1%)

**Table 4.** Associations of MCM7 and Ki-67 With Clinicopathological Characteristics
Variables	MCM7 LIs	Ki-67 LIs
SI: small intestine. LIs: labeling indices (%). Tests of significance: Mann-Whitney and Kruskal-Wallis tests. P-value ≤ 0.05 is considered significant.
Age			0.874			0.825
< 57 years	15.90 ± 9.68	12 (3 - 38)		8.05 ± 6.90	6 (0 - 20)
≥ 57 years	15.52 ± 12.52	13 (0 - 60)		7.82 ± 7.36	6 (0 - 33)
Gender			0.216			0.101
Male	17.91 ± 13.45	19 (0 - 60)		9.70 ± 8.52	9 (0 - 33)
Female	12.89 ± 6.67	12 (4 - 30)		5.68 ± 3.78	5 (0 - 13)
Tumor location			0.926			0.829
Gastric	16.75 ± 13.08	14 (0 - 60)		8.50 ± 7.66	7 (0 - 33)
SI	13.85 ± 6.31	12 (5 - 26)		7.00 ± 6.11	5 (0 - 19)
Colon	12	12		5	5
Tumor type			0.288			0.099
Spindle	15.08 ± 12.13	12 (0 - 60)		7.08 ± 7.25	5 (0 - 33)
Epithelioid	16.83 ± 7.16	17 (7 - 25)		9.50 ± 5.82	8 (4 - 19)
Mixed	15.69 ± 11.16	18(18 - 25)		14.33 ± 4.04	15 (10 - 18)
Tumor size			0.001			0.003
≤ 5 cm	10.66 ± 2.30	12 (8 - 12)		2.66 ± 2.30	4 (0 - 4)
> 5 - 10 cm	7.27 ± 6.52	6 (0 - 23)		3.54 ± 4.52	4 (0 - 15)
>10 cm	19.41 ± 11.24	18 (5 - 60)		10.13 ± 7.19	10 (0 - 33)
Tumor mitotic rate			< 0.001			< 0.001
≤ 5/50 HPF	9.66 ± 5.56	10 (0 - 20)		3.62 ± 3.29	4 (0 - 10)
> 5/50 HPF	23.31 ± 11.88	23 (9 - 60)		13.36 ± 6.84	13 (4 - 33)
Risk			< 0.001			< 0.001
Low	5.00 ± 3.84	5 (0 - 12)		2.00 ± 2.44	0 (0 - 6)
Intermediate	12.63 ± 4.41	12 (5 - 20)		4.36 ± 3.32	5 (0 - 10)
High	21.34 ± 11.78	20 (5 - 60)		11.95 ± 7.11	12 (0 - 33)
Metastasis			0.132			0.381
Yes	18.75 ± 8.37	19 (5 - 30)		9.12 ± 5.71	10 (0 - 19)
No	15.00 ± 11.69	12 (0 - 60)		7.65 ± 7.39	5 (0 - 33)
DOG1 score			0.339			0.123
Score 0, 1, 2	15.36 ± 13.56	12 (0 - 60)		6.89 ± 8.40	4 (0 - 33)
Score 3, 4	15.95 ± 9.12	13 (0 - 38)		8.75 ± 5.86	7 (0 - 20)
C-KIT score			0.548			0.572
Score 0, 1, 2	15.60 ± 12.60	12 (0 - 60)		7.75 ± 7.78	5 (0 - 33)
Score 3, 4	15.86 ± 8.19	13 (5 - 33)		8.26 ± 5.75	6 (0 - 20)

Table 4. Associations of MCM7 and Ki-67 With Clinicopathological Characteristics

Variables

MCM7 LIs

Ki-67 LIs

Mean ± SD

Median (min-max)

P-value

Mean ± SD

Median (min-max)

P-value

SI: small intestine. LIs: labeling indices (%). Tests of significance: Mann-Whitney and Kruskal-Wallis tests. P-value ≤ 0.05 is considered significant.

Age

0.874

0.825

< 57 years

15.90 ± 9.68

12 (3 - 38)

8.05 ± 6.90

6 (0 - 20)

≥ 57 years

15.52 ± 12.52

13 (0 - 60)

7.82 ± 7.36

6 (0 - 33)

Gender

0.216

0.101

Male

17.91 ± 13.45

19 (0 - 60)

9.70 ± 8.52

9 (0 - 33)

Female

12.89 ± 6.67

12 (4 - 30)

5.68 ± 3.78

5 (0 - 13)

Tumor location

0.926

0.829

Gastric

16.75 ± 13.08

14 (0 - 60)

8.50 ± 7.66

7 (0 - 33)

13.85 ± 6.31

12 (5 - 26)

7.00 ± 6.11

5 (0 - 19)

Colon

Tumor type

0.288

0.099

Spindle

15.08 ± 12.13

12 (0 - 60)

7.08 ± 7.25

5 (0 - 33)

Epithelioid

16.83 ± 7.16

17 (7 - 25)

9.50 ± 5.82

8 (4 - 19)

Mixed

15.69 ± 11.16

18(18 - 25)

14.33 ± 4.04

15 (10 - 18)

Tumor size

0.001

0.003

≤ 5 cm

10.66 ± 2.30

12 (8 - 12)

2.66 ± 2.30

4 (0 - 4)

> 5 - 10 cm

7.27 ± 6.52

6 (0 - 23)

3.54 ± 4.52

4 (0 - 15)

>10 cm

19.41 ± 11.24

18 (5 - 60)

10.13 ± 7.19

10 (0 - 33)

Tumor mitotic rate

< 0.001

≤ 5/50 HPF

9.66 ± 5.56

10 (0 - 20)

3.62 ± 3.29

4 (0 - 10)

> 5/50 HPF

23.31 ± 11.88

23 (9 - 60)

13.36 ± 6.84

13 (4 - 33)

Risk

< 0.001

Low

5.00 ± 3.84

5 (0 - 12)

2.00 ± 2.44

0 (0 - 6)

Intermediate

12.63 ± 4.41

12 (5 - 20)

4.36 ± 3.32

5 (0 - 10)

High

21.34 ± 11.78

20 (5 - 60)

11.95 ± 7.11

12 (0 - 33)

Metastasis

0.132

0.381

Yes

18.75 ± 8.37

19 (5 - 30)

9.12 ± 5.71

10 (0 - 19)

15.00 ± 11.69

12 (0 - 60)

7.65 ± 7.39

5 (0 - 33)

DOG1 score

0.339

0.123

Score 0, 1, 2

15.36 ± 13.56

12 (0 - 60)

6.89 ± 8.40

4 (0 - 33)

Score 3, 4

15.95 ± 9.12

13 (0 - 38)

8.75 ± 5.86

7 (0 - 20)

C-KIT score

0.548

0.572

Score 0, 1, 2

15.60 ± 12.60

12 (0 - 60)

7.75 ± 7.78

5 (0 - 33)

Score 3, 4

15.86 ± 8.19

13 (5 - 33)

8.26 ± 5.75

6 (0 - 20)