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 364-374

Correlation of NQO1 and Nrf2 in Female Genital Tract Cancer and Their Precancerous Lesions (Cervix, Endometrium and Ovary)

Figure 1. NQO1 protein expression in different lesions using IHC (× 400, DAB was used as the chromogen and hematoxylin as counterstain). (a) NQO1 protein was weak in normal cervical epithelium. (b) NQO1 protein staining was moderate positive in LSIL. (c) NQO1 protein showed diffuse and strong cytoplasmic-positive staining in HSIL. (d) NQO1 was strong positive in grade I cervical SCC. (e) NQO1 protein was weak in proliferative endometrium. (f) NQO1 was moderate positive in simple EH. (g) NQO1 was strong positive in atypical EH. (h) NQO1 was strong positive in EC. (i) NQO1 was negative in normal ovarian epithelium. (j) NQO1 was positive mucinous cystadenoma. (k) NQO1 was moderate positive in borderline serous tumor. (l) NQO1 was strong positive in ovarian carcinoma.

Figure 2. Nrf2 protein expression in different lesions using IHC (× 400, DAB was used as the chromogen and hematoxylin as counterstain). (a) Nrf2 protein was weak in normal cervical epithelium. (b) Nrf2 protein staining was moderate positive in LSIL. (c) Nrf2 protein showed moderate nuclear-positive staining in HSIL, but weak positive in adjacent normal cervical glands. (d) Nrf2 was strong positive in grade II cervical SCC. (e) Nrf2 protein was positive in proliferative endometrium. (f) Nrf2 was moderate positive in simple EH. (g) Nrf2 was moderate positive in atypical EH. (h) Nrf2 was strong positive in EC. (i) Nrf2 was negative in normal ovarian epithelium. (j) Nrf2 was positive serous cystadenoma. (k) Nrf2 was moderate positive in borderline serous tumor. (l) Nrf2 was strong positive in ovarian carcinoma.

Figure 3. NQO1 expression box plots (a) in different cervical lesions; (b) in different endometrial lesions; (c) in different ovarian lesions. Horizontal lines in the boxes represent the median value of each group. The top and bottom edges of the boxes indicate the score values from 75th percentile and the 25th percentile respectively. Whiskers represent the highest and lowest values. The range is shown as a vertical line.

Figure 4. NrF2 expression box plots (a) in different cervical lesions; (b) in different endometrial lesions; (c) in different ovarian lesions. Horizontal lines in the boxes represent the median value of each group. The top and bottom edges of the boxes indicate the score values from 75th percentile and the 25th percentile respectively. Whiskers represent the highest and lowest values. The range is shown as a vertical line.

**Table 1.** Positive Expression Rates, Mean Values and SDs for NQO1 in Different Lesions With Examined Sites
Site	Lesion	No.	% +ve	Mean ± SD	Min	Max	P-value among groups
Test of significance: Kruskal-Wallis, Mann-Whitney test. Normal vs. SIL, P = 0.091; normal vs. carcinoma, P < 0.001; SIL vs. carcinoma, P = 0.004. Cyclic endometrium vs. hyperplasia, P = 0.402; cyclic endometrium vs. carcinoma, P = 0.007; hyperplasia vs. carcinoma, P = 0.003. **Normal vs. benign, P = 0.005; normal vs. borderline, P = 0.003; normal vs. carcinoma, P < 0.001; benign vs. borderline, P = 0.554; benign vs. carcinoma, P = 0.006; borderline vs. carcinoma, P = 0.076.
Cervix*	Normal	10	20	3.70 ± 5.01	0	15	< 0.001
SIL	20	45	18.35 ± 24.94	0	80
Carcinoma	50	76	44.34 ± 29.52	0	90
Endometrium**	Cyclic endometrium	10	10	2.40 ± 3.30	0	10	0.001
Hyperplasia	20	30	10.15 ± 15.61	0	50
Carcinoma	50	60	36.92 ± 31.94	0	85
Ovary***	Normal	10	0	0	0	0	< 0.001
Benign	20	20	6.30 ± 9.88	0	30
Borderline	20	25	12.40 ± 21.08	0	60
Carcinoma	50	56	28.30 ± 27.29	0	80

Table 1. Positive Expression Rates, Mean Values and SDs for NQO1 in Different Lesions With Examined Sites

Site

Lesion

No.

% +ve

Mean ± SD

Min

Max

P-value among groups

Test of significance: Kruskal-Wallis, Mann-Whitney test. *Normal vs. SIL, P = 0.091; normal vs. carcinoma, P < 0.001; SIL vs. carcinoma, P = 0.004. **Cyclic endometrium vs. hyperplasia, P = 0.402; cyclic endometrium vs. carcinoma, P = 0.007; hyperplasia vs. carcinoma, P = 0.003. ***Normal vs. benign, P = 0.005; normal vs. borderline, P = 0.003; normal vs. carcinoma, P < 0.001; benign vs. borderline, P = 0.554; benign vs. carcinoma, P = 0.006; borderline vs. carcinoma, P = 0.076.

Cervix*

Normal

3.70 ± 5.01

< 0.001

SIL

18.35 ± 24.94

Carcinoma

44.34 ± 29.52

Endometrium**

Cyclic endometrium

2.40 ± 3.30

0.001

Hyperplasia

10.15 ± 15.61

Carcinoma

36.92 ± 31.94

Ovary***

Normal

< 0.001

Benign

6.30 ± 9.88

Borderline

12.40 ± 21.08

Carcinoma

28.30 ± 27.29

**Table 2.** Positive Expression Rates, Mean Values and SDs for Nrf2 in Different Lesions With Examined Organs
Organ	Lesion	No.	% +ve	Mean ± SD	Min	Max	P-value among groups
Test of significance: Kruskal-Wallis, Mann-Whitney test. Normal vs. SIL, P = 0.155; normal vs. carcinoma, P = 0.002; SIL vs. carcinoma, P = 0.005. Cyclic endometrium vs. hyperplasia, P = 0.350; cyclic endometrium vs. carcinoma, P = 0.009; hyperplasia vs. carcinoma, P < 0.005. **Normal vs. benign, P = 0.015; normal vs. borderline, P = 0.003; normal vs. carcinoma, P < 0.001; benign vs. borderline, P = 0.529; benign vs. carcinoma, P = 0.005; borderline vs. carcinoma, P = 0.029.
Cervix*	Normal	10	10	4.60 ± 5.42	0	15	0.001
SIL	20	30	14.50 ± 18.20	0	60
Carcinoma	50	62	39.24 ± 29.25	0	85
Endometrium**	Cyclic endometrium	10	10	4.30 ± 6.01	0	20	0.001
Hyperplasia	20	35	12.20 ± 16.91	0	60
Carcinoma	50	64	39.82 ± 32.65	0	85
Ovary***	Normal	10	0	0	0	0	< 0.001
Benign	20	25	10.30 ± 14.50	0	50
Borderline	20	20	14.60 ± 19.33	0	60
Carcinoma	50	72	32.70 ± 29.44	0	85

Table 2. Positive Expression Rates, Mean Values and SDs for Nrf2 in Different Lesions With Examined Organs

Organ

Lesion

No.

% +ve

Mean ± SD

Min

Max

P-value among groups

Test of significance: Kruskal-Wallis, Mann-Whitney test. *Normal vs. SIL, P = 0.155; normal vs. carcinoma, P = 0.002; SIL vs. carcinoma, P = 0.005. **Cyclic endometrium vs. hyperplasia, P = 0.350; cyclic endometrium vs. carcinoma, P = 0.009; hyperplasia vs. carcinoma, P < 0.005. ***Normal vs. benign, P = 0.015; normal vs. borderline, P = 0.003; normal vs. carcinoma, P < 0.001; benign vs. borderline, P = 0.529; benign vs. carcinoma, P = 0.005; borderline vs. carcinoma, P = 0.029.

Cervix*

Normal

4.60 ± 5.42

0.001

SIL

14.50 ± 18.20

Carcinoma

39.24 ± 29.25

Endometrium**

Cyclic endometrium

4.30 ± 6.01

0.001

Hyperplasia

12.20 ± 16.91

Carcinoma

39.82 ± 32.65

Ovary***

Normal

< 0.001

Benign

10.30 ± 14.50

Borderline

14.60 ± 19.33

Carcinoma

32.70 ± 29.44

**Table 3.** Associations Between NQO1 and Nrf2 Expression Scores and Clinicopathological Data in Carcinoma Cases
Organ	Clinicopathological parameter	No. of cases	NQO1	Nrf2
Test of significance: Kruskal-Wallis, ANOVA tests. P-value < 0.05 is considered significant.
Cervix	Age
Mean	55.20 ± 6.54	44.34 ± 29.52	0.445	39.24 ± 29.25	0.526
Grade
I	14	25.14 ± 33.26	0.045	25.14 ± 33.03	0.016
II	20	26.80 ± 29.65		28.00 ± 29.11
III	16	33.50 ± 32.61		23.00 ± 23.59
Stage
I	8	40.62 ± 37.74	0.461	36.88 ± 32.28	0.594
II	28	48.32 ± 29.80		35.11 ± 29.01
III	10	42.40 ± 25.57		48.50 ± 28.67
IV	4	28.75 ± 20.15		49.75 ± 29.89
Endometrium	Age
Mean	51.90 ± 5.77	36.92 ± 31.94	0.802	39.82 ± 55.00	0.923
Grade
I	16	17.25 ± 27.14	0.011	18.44 ± 28.61	0.002
II	21	45.38 ± 31.39		48.48 ± 31.35
III	23	47.46 ± 28.99		52.15 ± 28.06
Stage
I	10	12.60 ± 23.98	0.082	13.40 ± 24.73	0.025
II	13	40.69 ± 32.61		41.54 ± 31.31
III	19	42.00 ± 31.28		49.11 ± 33.18
IV	8	49.13 ± 30.82		48.00 ± 29.21
Ovary	Age
Mean	55.74 ± 9.92	28.30 ± 27.29	0.734	32.70 ± 29.44	0.395
Grade
I	10	22.70 ± 30.31	0.712	30.80 ± 37.00	0.576
II	23	26.87 ± 26.72		29.26 ± 30.14
III	17	33.53 ± 27.02		18.47 ± 24.10
Stage
I	8	12.50 ± 21.66	0.167	16.88 ± 28.77	0.020
II	15	22.53 ± 30.07		19.80 ± 31.06
III	15	33.47 ± 25.14		45.27 ± 25.06
IV	12	39.58 ± 25.71		43.67 ± 23.50

Table 3. Associations Between NQO1 and Nrf2 Expression Scores and Clinicopathological Data in Carcinoma Cases

Organ

Clinicopathological parameter

No. of cases

NQO1

Nrf2

Mean ± SD

P-value

Mean ± SD

P-value

Test of significance: Kruskal-Wallis, ANOVA tests. P-value < 0.05 is considered significant.

Cervix

Age

Mean

55.20 ± 6.54

44.34 ± 29.52

0.445

39.24 ± 29.25

0.526

Grade

25.14 ± 33.26

0.045

25.14 ± 33.03

0.016

26.80 ± 29.65

28.00 ± 29.11

III

33.50 ± 32.61

23.00 ± 23.59

Stage

40.62 ± 37.74

0.461

36.88 ± 32.28

0.594

48.32 ± 29.80

35.11 ± 29.01

III

42.40 ± 25.57

48.50 ± 28.67

28.75 ± 20.15

49.75 ± 29.89

Endometrium

Age

Mean

51.90 ± 5.77

36.92 ± 31.94

0.802

39.82 ± 55.00

0.923

Grade

17.25 ± 27.14

0.011

18.44 ± 28.61

0.002

45.38 ± 31.39

48.48 ± 31.35

III

47.46 ± 28.99

52.15 ± 28.06

Stage

12.60 ± 23.98

0.082

13.40 ± 24.73

0.025

40.69 ± 32.61

41.54 ± 31.31

III

42.00 ± 31.28

49.11 ± 33.18

49.13 ± 30.82

48.00 ± 29.21

Ovary

Age

Mean

55.74 ± 9.92

28.30 ± 27.29

0.734

32.70 ± 29.44

0.395

Grade

22.70 ± 30.31

0.712

30.80 ± 37.00

0.576

26.87 ± 26.72

29.26 ± 30.14

III

33.53 ± 27.02

18.47 ± 24.10

Stage

12.50 ± 21.66

0.167

16.88 ± 28.77

0.020

22.53 ± 30.07

19.80 ± 31.06

III

33.47 ± 25.14

45.27 ± 25.06

39.58 ± 25.71

43.67 ± 23.50