Expression of phosphorylated Hippo pathway kinases (MST1/2 and LATS1/2) in HER2-positive and triple-negative breast cancer patients treated with neoadjuvant therapy

Figures & data

Table 1. Baseline characteristics of breast cancer patients included in this study (n = 57).

	N	%
Age at diagnosis
Median (IQR)	50 (21)
Menopausal status
Yes	30	53
No	27	47
Clinical Stage
II A	17	30
II B	17	30
III A	15	26
III B	6	11
III C	2	3
Grade
G1-G2	11	19
G3	46	81
Ki-67 Median
Low (<35%)	26	46
High (≥35%)	31	54
Ki-67
<14%	2	4
≥14%	55	96
Molecular Subtype
Luminal B	15	26
HER2-enriched	15	26
Triple-Negative	27	48
Stromal TIL
< 50%	49	86
≥ 50%	8	14
pCR (pT0/is - N0)
Yes	28	49
No	29	51
pCR (pT0 – N0)
Yes	23	40
No	34	60

Figure 1. Representative examples of immunohistochemical expression of pMST1/2 and pLATS1/2 in 4 breast cancer cases (a,b,c,d). Panels a and b show 2 cases with cytoplasmic pMST1/2 (a) and cytoplasmic pLATS1/2 (b) expression with concomitant expression in stromal TILs. Panels c and d show 2 cases with nuclear pMST1/2 (c) and nuclear pLATS1/2 (d) expression with concomitant expression in stromal TILs. Slide magnification x 40, inset magnification x 20. Scale bar 30 μm.

Table 2. expression pattern of pMST1/2 and pLATS1/2 in HER2-positive and triple-negative breast cancer (n = 57).

	N	%
pLATS1/2 stromal TILs
Negative	33	58
Positive, Range (10%–80%)	24	42
pLATS1/2 nuclear
Negative	12	21
Positive, Range (10%–80%)	45	78
pLATS1/2 cytoplasm
Negative	49	86
Positive, Range (50%–80%)	8	14
pMST1/2 stromal TILs
Negative	43	75
Positive, Range (10%–80%)	14	25
pMST1/2 nuclear
Negative	32	56
Positive, Range (10%–80%)	25	44
pMST1/2 cytoplasm
Negative	32	56
Positive, Range (60%–80%)	25	44

Table 3. Significant or borderline significant associations between the molecular markers of interest (pMST1/2 and pLATS1/2) and clinical-pathological factors.

	pMST1/2^cyt
	Negative	Positive	p-value
	N (%)	N (%)
Molecular Subtype
TNBC	20 (74)	12 (40)	0.010°
Her2-positive	7 (26)	18 (60)
	pLATS1/2^cyt
Grade
G1-G2	7 (14)	4 (50)	0.037°°
G3	42 (86)	4 (50)
	pMST1/2^nuc
Molecular Subtype
TNBC	9 (33)	23 (77)	0.001°
Her2-positive	18 (67)	7 (23)
	pMST1/2 stromal TILs
Age at diagnosis
(median (years); min-max)	54 (27–77)	43 (35–77)	0.012^*
Menopausal Status
Pre	16 (37)	11 (79)	0.012°°
Post	27 (63)	3 (21)
Molecular Subtype
TNBC	17 (40)	10 (71)	0.063°°
Her2-positive	26 (60)	4 (29)
	pLATS1/2 stromal TILs
Age at diagnosis
(median (years); min-max)	55 (27–76)	48 (27–77)	0.047^*
Menopausal Status
Pre	10 (33)	17 (63)	0.025°
Post	20 (67)	10 (37)
Ki-67
Low	19 (63)	7 (26)	0.005°
High	11 (37)	20 (74)
Molecular Subtype
TNBC	8 (27)	19 (70)	0.001°
Her2-positive	22 (73)	8 (30)

* Mann-Whitney test; °Chi2 test; °° Fisher-exact test

Figure 2. Bar charts illustrating the association between pMST1/2^cyt and TAZ (panel A), and between pMST1/2^nuc and pChk1 (panel B).

Table 4. Relationship between pMST1/2 expression and pCR (n=57).

	pCR (pT0/is pN0)
	Yes	No	p-value
pMST1/2^nuc
Negative	21 (66%)	11 (34%)	0.005
Positive	7 (28%)	18 (72%)
pMST1/2^cyt
Negative	12 (37%)	20 (63%)	0.047
Positive	16 (64%)	9 (36%)
	pCR (pT0 pN0)
	Yes	No	p-value
pMST1/2^nuc
Negative	17 (53%)	15 (47%)	0.026
Positive	6 (24%)	19 (76%)
pMST1/2^cyt
Negative	9 (28%)	23 (72%)	0.033
Positive	14 (56%)	11 (44%)

Figure 3. Univariate regression models for pCR (pT0/is pN0 and pT0 pN0) illustrating OR and 95%CI: clinical-molecular variables are reported including stage (III vs II), grade (G3 vs G1–2), Ki-67 levels (high vs low), molecular subtypes (HER2-positive vs triple-negative), pMST1/2^cyt (positive vs negative) and pMST1/2^nuc (positive vs negative).