J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Original Article

Volume 14, Number 10, October 2022, pages 416-424

STAT-5 and STAT-6 in Breast Cancer: Potential Crosstalk With Estrogen and Progesterone Receptors Can Affect Cell Proliferation and Metastasis

Figure 1. Relative mRNA expression levels of STAT5a and STAT6 according to clinical and molecular information. STAT: signal transducers and activators of transcription; SBR: Scarff-Bloom-Richardson.

Figure 2. Immunochemical staining with anti-HER2 and anti-Ki-67 antibodies in breast tumors. (a) Presence of overexpression of HER2 oncoprotein (HER2 score: 3; original magnification, × 400). (b) Ki-67 proliferation index estimated at 70% (original magnification, × 250).

Figure 3. Relative mRNA expression level of STAT5a and STAT6 according to clinical and molecular information. (a) STAT5a mRNA expression level in (STAT5a+, ERα+) subgroup. (b) STAT5a mRNA expression level in (STAT5a+, ERβ+) subgroups. (c) STAT5a mRNA expression level in (STAT5a+, PR+) subgroups. (d) STAT6 mRNA expression level in (STAT6+, ERα+) subgroup. (e) STAT6 mRNA expression level in (STAT6+, ERβ+) subgroup. (f) STAT6 mRNA expression level in (STAT6+, PR+) subgroup. STAT: signal transducers and activators of transcription; ER: estrogen receptor; PR: progesterone receptor; SBR: Scarff-Bloom-Richardson.

**Table 1.** Relationship Between the mRNA STAT5a and STAT6 Expressions and the Standard Clinical and Pathological Factors and Molecular Settings
Characteristics	Total population	STAT5a	P value	STAT6	P value^a
^aChi-square test in R. ^bScarff-Bloom-Richardson classification. STAT: signal transducers and activators of transcription; SBR: Scarff-Bloom-Richardson; NS: not significant.
Total	40 (100%)	5 (12.5)	35 (87.5)		9 (22.50)	31 (77.50)
Menopausal status
Pre-	15 (37.5)	0 (0.0)	15 (42.85)		1 (11.11)	14 (45.16)
Post-	25 (62.5)	5 (100)	20 (57.14)	NS	8 (88.88)	17 (54.83)	NS
Grade^b
SBRI	9 (21.87)	3 (60)	6 (17.14)		5 (55.55)	4 (12.90)
SBRII	21 (52.50)	0 (0.00)	21 (60.00)	0.0005	4 (44.44)	17 (54.83)	0.002
SBRIII	10 (25)	2 (40)	8 (22.85)		0 (0.0)	10 (32.25)
Lymph node status
Positive	21 (52.50)	2 (40)	19 (54.28)		0 (100.0)	21 (67.74)
Negative	19 (47.50)	3 (60)	16 (45.71)	NS	9 (100)	10 (32.25)	0.01
Tumor size
≤ 30 mm	27 (67.50)	1 (20)	26 (74.28)	0.0001	4 (44.44)	23 (74.19)	0.0003
> 30 mm	13 (32.50)	4 (80)	9 (25.71)		5 (55.55)	8 (25.80)

HER2 status
Positive	10 (25)	0 (00)	10 (28.57)		1 (11.11)	9 (29.03)
Negative	30 (75)	5 (100)	25 (71.42)	0.0008	8 (88.88)	22 (70.96)	0.002
Ki67
≤ 14%	15(37.50)	2 (40)	13 (42.85)		2 (22.22)	13 (41.93)
> 14%	25 (62.50)	3 (60)	22 (57.14)	NS	7 (77.77)	18 (58.06)	NS

Table 1. Relationship Between the mRNA STAT5a and STAT6 Expressions and the Standard Clinical and Pathological Factors and Molecular Settings

Characteristics

Total population

STAT5a

P value

STAT6

P value^a

Negative (%)

Positive (%)

Negative (%)

Positive (%)

^aChi-square test in R. ^bScarff-Bloom-Richardson classification. STAT: signal transducers and activators of transcription; SBR: Scarff-Bloom-Richardson; NS: not significant.

Total

40 (100%)

5 (12.5)

35 (87.5)

9 (22.50)

31 (77.50)

Menopausal status

Pre-

15 (37.5)

0 (0.0)

15 (42.85)

1 (11.11)

14 (45.16)

Post-

25 (62.5)

5 (100)

20 (57.14)

8 (88.88)

17 (54.83)

Grade^b

SBRI

9 (21.87)

3 (60)

6 (17.14)

5 (55.55)

4 (12.90)

SBRII

21 (52.50)

0 (0.00)

21 (60.00)

0.0005

4 (44.44)

17 (54.83)

0.002

SBRIII

10 (25)

2 (40)

8 (22.85)

0 (0.0)

10 (32.25)

Lymph node status

Positive

21 (52.50)

2 (40)

19 (54.28)

0 (100.0)

21 (67.74)

Negative

19 (47.50)

3 (60)

16 (45.71)

9 (100)

10 (32.25)

0.01

Tumor size

≤ 30 mm

27 (67.50)

1 (20)

26 (74.28)

0.0001

4 (44.44)

23 (74.19)

0.0003

> 30 mm

13 (32.50)

4 (80)

9 (25.71)

5 (55.55)

8 (25.80)

HER2 status

Positive

10 (25)

0 (00)

10 (28.57)

1 (11.11)

9 (29.03)

Negative

30 (75)

5 (100)

25 (71.42)

0.0008

8 (88.88)

22 (70.96)

0.002

Ki67

≤ 14%

15(37.50)

2 (40)

13 (42.85)

2 (22.22)

13 (41.93)

> 14%

25 (62.50)

3 (60)

22 (57.14)

7 (77.77)

18 (58.06)

**Table 2.** Relationship Between the STAT5a, STAT6 and ERα, ERβ and PR Expressions in Mammary Malign Tumors
	STAT5a+ (n = 35)	P value	STAT6+ (n = 31)	P value
STAT: signal transducers and activators of transcription; ER: estrogen receptor; PR: progesterone receptor.
ERα+	24/35	0.004	21/31	0.01
ERβ+	23/35	0.01	20/31	0.04
PR+	27/35	0.0000168	25/31	0.00000483

Table 2. Relationship Between the STAT5a, STAT6 and ERα, ERβ and PR Expressions in Mammary Malign Tumors

STAT5a+ (n = 35)

P value

STAT6+ (n = 31)

P value

STAT: signal transducers and activators of transcription; ER: estrogen receptor; PR: progesterone receptor.

ERα+

24/35

0.004

21/31

0.01

ERβ+

23/35

0.01

20/31

0.04

PR+

27/35

0.0000168

25/31

0.00000483

**Table 3.** Coexpression of STAT5a With ERα, ERβ and PR and the Relationship With Clinical and Molecular Settings
	STAT5a+
STAT: signal transducers and activators of transcription; ER: estrogen receptor; PR: progesterone receptor; SBR: Scarff-Bloom-Richardson; NS: not significant.
Menopausal status
Pre-	10		9		11
Post-	14	NS	14	NS	16	NS
SBR grade
I	5	0.0001	4	0.0000365	5	0.0000133
II + III	19		19		22
Lymph node status
N+	13	NS	16	0.01	16	NS
N-	11		7		11
KI67
> 14	16	0.04	15	NS	19	0.006
≤ 14	8		9		8
HER2
+	7		5		6
-	17	0.009	18	0.0004	21	0.0001

Table 3. Coexpression of STAT5a With ERα, ERβ and PR and the Relationship With Clinical and Molecular Settings

STAT5a+

ERα+ (n = 24)

P value

ERβ+ (n = 23)

P value

PR+ (n = 27)

P value

STAT: signal transducers and activators of transcription; ER: estrogen receptor; PR: progesterone receptor; SBR: Scarff-Bloom-Richardson; NS: not significant.

Menopausal status

Pre-

Post-

SBR grade

0.0001

0.0000365

0.0000133

II + III

Lymph node status

N+

0.01

N-

KI67

> 14

0.04

0.006

≤ 14

HER2

0.009

0.0004

0.0001

**Table 4.** Coexpression of STAT6 With ERα, ERβ and PR and the Relationship With Clinical and Molecular Settings
	STAT6+
STAT: signal transducers and activators of transcription; ER: estrogen receptor; PR: progesterone receptor; SBR: Scarff-Bloom-Richardson; NS: not significant.
Menopausal status
Pre-	9	NS	7	NS	12	NS
Post-	12		13		13
SBR grade
I	3	0.0000177	4	0.0005	6	0.0006
II + III	18		16		19
Lymph node status
N+	13	NS	15	0.004	17	0.02
N-	8		5		8
KI67
> 14	15	0.01	12	NS	18	0.004
≤ 14	6		8		7
HER2
+	16		16		6
-	5	0.002	4	0.0005	19	0.0006

Table 4. Coexpression of STAT6 With ERα, ERβ and PR and the Relationship With Clinical and Molecular Settings

STAT6+

ERα+ (n = 21)

P value

ERβ+ (n = 20)

P value

PR+ (n = 25)

P value

STAT: signal transducers and activators of transcription; ER: estrogen receptor; PR: progesterone receptor; SBR: Scarff-Bloom-Richardson; NS: not significant.

Menopausal status

Pre-

Post-

SBR grade

0.0000177

0.0005

0.0006

II + III

Lymph node status

N+

0.004

0.02

N-

KI67

> 14

0.01

0.004

≤ 14

HER2

0.002

0.0005

0.0006