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. 2022 Apr 21;17(3):223–252. doi: 10.1007/s11523-022-00876-z

Table 5.

Molecular aberrations in desmoid tumours: retrospective case-series

Author Patients and samples (recurrence) Mean age, range (years) Sex (F/M) (%) Sporadic status (%) Tumour location (%) Mean tumour size, range (cm) Molecular target Results Significance
Matono et al. [24]

63 patients

74 samples (11)

34.2,

0–76

 65/35 100

E-AD: 67

AD: 19

I-AD: 14

 NS IHC: n (%)
β-catenin (n > 50% 35/74 (56) p = 0.04a
VEGF > 10% 47/74 (73)
MVD: mean ± SD
VEGF ( +) 10.62 ± 4.41 p = 0.84b
VEGF (−) 9.55 ± 3.96
Recurrent tumour 13.97 ± 5.32 p = 0.02b
Primary tumour 9.56 ± 3.72
Ferenc et al. [25]

33 patients

35 samples (2)

33.5,

15–68

 86/14 100

E-AD: 43

AD: 57

5,

2–12

3 missing

 IHC: n (%)
α-catenin (c) ≥ 10%

E-AD: 10/15 (67)

AD: 13/20 (65)

 –
α-catenin (c) (–)

E-AD: 5/15 (33)

AD: 7/20 (35)

 –
β-catenin (c) ≥ 10%

E-AD: 14/15 (93)

AD: 17/20 (85)

 –
β-catenin (n ≥ 10%

E-AD: 8/15 (53)

AD: 15/20 (75)

 –
β-catenin (c + n) ≥ 10%

E-AD: 7/15 (47)

AD: 12/20 (60)

 –
N-Cadherin (c) ≥ 10%

E-AD: 4/15 (27)

AD: 4/20 (20)

 –
IHC: % mean immunoreactive cells
α-catenin (c)

E-AD: 61.5

AD: 42.3

 p = 0.0165c
β-catenin (c)

E-AD: 51.3

AD: 35.5

 p > 0.05c
β-catenin (n

E-AD: 24.7

AD: 32.5

 p > 0.05c
β-catenin (c + n)

E-AD: 24.0

AD: 26.0

 p > 0.05c
N-cadherin (c)

E-AD: 55.0

AD: 42.5

 p > 0.05c
Correlation: r
β-catenin (n) and α-catenin −0.0363 p = 0.9207e
β-catenin (n) and N-cadherin −0.7510 p = 0.2490e
Jilong et al. [26]

99 patients (14)

69 samples

30.5†,

8–86

 77/23 100

E-AD: 45

AD: 35

I-AD: 20

 NS Gene sequencing: n (%)
CTNNB1 T41A 13/69 (18.8) –
CTNNB1 WT 56/69 (81.2)
CTNNB1 T41A and CCND1 > 10% 9/13 (69.2)

χ2 = 4.323

p = 0.038d
CTNNB1 WT and CCND1 > 10% 21/56 (37.5)
IHC: n (%)
β-catenin (c +n) > 10% 33/69 (47.8)
c-myc > 10% 31/69 (44.9)
Cyclin D1 > 10% 30/69 (43.5)
β-catenin ( +) and c-myc > 10% 23/33 (69.7)

χ2 = 15.68

p = 0.001d
β-catenin (−) and c-myc > 10% 8/36 (22.2)
AI: n, mean ± SD
β-catenin (c +n) > 10% 33, 0.019 ± 0.008

t = 1.72

p = 0.09c
β-catenin (c +n) (–) 36, 0.023 ± 0.009
c-myc > 10% 31, 0.019 ± 0.007

t = 2.78

p = 0.007c
c-myc (–) 38, 0.024 ± 0.010
Cyclin-D1 > 10% 30, 0.018 ± 0.009

t = 2.495

p = 0.015c
Cyclin D1 (–) 39, 0.024 ± 0.010
Stalinska et al. [56] 18 samples NS NS NS E-AD: 100 NS IHC: n (%)
pRb > 50% 17/18 (94.4) –
pRb 10–50% 1/18 (5.56) –
p16 > 50% 9/18 (50) –
p16 10-50% 9/18 (50) –
PCNA > 50% 18/18 (100) –
Ki-67 > 50% 0/18 (0) –
Ki-67 (−) 15/18 (83.33) –
MCM5 > 50% 0/18 (0) –
MCM5 (−) 18/18 (100) –
IHC: % mean immunoreactive cells
pRb 73.87 –
P16 46.32 –
PCNA 79.26 –
Ki-67 7.54 –
MCM5 0.00 –
Saito et al. [27] 38 samples NS NS 100

E-AD: 74

AD: 26

 NS IHC: n (%)
β-catenin (n) > 75% 19/38 (50) –
Cyclin D1 > 5% 27/38 (71.1) –
β-catenin (n) and cyclin D1 17/19 (89.5) p = 0.029a
β-catenin (−) and cyclin D1 10/19 (52.6)
IHC: mean (range)
MIB-1-LI 3.0 (0–28.6) –
PCNA-LI 31.8 (2.5–67.4) –
IHC: n, mean (SD)
MIB-1-LI and β-catenin (n) – p >  0.05a
MIB-1-LI and cyclin D1 – p > 0.05a
PCNA-LI and β-catenin (n) 19, 37.9 (14.1) p = 0.007a
PCNA-LI and cyclin-D1 ( +) 27, 35.9 (13.6) p = 0.004a
Gene amplification: n (%)
CCND1 amplification 13/22 (59.1%) –
An et al. [28] 70 samples

36.01,

0.17–84

 59/41 NS

E-AD: 74

AD: 13

I-AD: 13

6.7,

0.9–17

 IHC: n (%)
β-catenin (n) > 1% 56/70 (80) –
CTNNB1 gene sequencing: n (%)
WT 27/70 (38.56) –
MT 43/70 (61.43) –
T41A 27/70 (62.79) –
T41I 1/70 (2.33) –
S45F 12/70 (27.91) –
S45P 2/70 (4.64) –
T41A and S45F 1/70 (2.33) –
WT and β-catenin (n) 17/27 (63.0) p = 0.012a
MT and β-catenin (n) 39/43 (90.7)
WT and size (cm; mean ± SD) 4.973 ± 0.952, n = 22 p = 0.020c
MT and size (cm; mean ± SD) 7.655 ± 0.642, n = 42
Matono et al. [29]

63 patients

74 samples (9)

34.2,

NS

 65/35 100

E-AD: 72

AD: 16

I-AD: 12

 NS IHC: n (%)
β-catenin (n) > 50% 35/63 (56) –
MMP7 > 50% 39/63 (62) –
Cyclin D1 > 5% 40/63 (63) –
β-catenin (n) and MMP7 32/63 (51) p < 0.1a
β-catenin (−) and MMP7 7/63 (11)
β-catenin (n) and cyclin D1 27/63 (43) p = 0.034a
β-catenin (−) and cyclin D1 13/63 (21)
mRNA expression: mean ± SD
MT CTNNB1 and MMP7 RNA 129.1 ± 111.8 p = 0.0018b
WT CTNNB1 and MMP7 RNA 33.9 ± 23.6
MT CTNNB1 and CCND1 RNA 29.7 ± 8.86 p = 0.019b
WT CTNNB1 and CCND1 RNA 6.8 ± 8.01
Signoroni et al. [39] 8 patients

43,

25–70

 37/63 100

E-AD: 50

AD: 50

 NS IHC: n (%)
COX-2 (c) 8/8 (100) –
PDGFRA (c) 8/8 (100) –
PDGFRB (c) 8/8 (100) –
mRNA expression: n (%)
PTGS2 (COX-2) 8/8 (100) –
Gene expression: real-time PCR (mean 2-ΔΔCt)
PDGFRA 3.4
PDGFRB 31.8
Immunoprecipitation and phosphorylation: n (%)
PDGFRA expression 8/8 (100) –
PDGFRA high expression 0/8 (100)
PDGFRB expression 8/8 (62.5) –
PDGFRB high expression 3/8 (37.5) –
Santti et al. [36] ERβ IHC: n (%)

83 patients

83 samples

< 35: 43

> 35: 40

 71/29 87

E-AD and AD: 88

I-AD: 11

Multifocal: 1

< 6: 26

> 6: 43

14 missing

 ERβ expression (%; median, IQR) 10.8, 31.1 –
ERβ > 1% 68/83 (82) –
Cyclin D1 expression (%; median, IQR) 15.6, 21.0 –
Cyclin D1 > 5% 63/77 (82) –
Cyclin D1 Cyclin D1 > 10% 49/77 (64) –

77 patients

77 samples

< 35: 38

> 35: 39

 69/31 87

E-AD and AD: 88

I-AD: 10

Multifocal: 2

< 6: 23

> 6: 42

12 missing

 Correlation: r
ERβ and cyclin D1 0.34 p = 0.004e
ERβ and Ki67 0.35 p = 0.003e
ERβ and cyclin A 0.40 p < 0.001e
Cyclin D1 and Ki67 0.40 p = 0.001e
Cyclin D1 and cyclin A 0.34 p = 0.004e
Deyrup et al. [45]

40 patients

40 samples

33.4,

5–74

 73/27 100 E-AD: 100 NS IHC: n (%)
ERβ > 50% 33/40 (83) –
ERβ 11–50% 5/40 (12) –
ERβ < 10% 2/40 (5) –
ERα 0/40 (0) –
Santos et al. [42]

59 patients

59 samples

< 50: 30

> 50: 29

 61/39 100

E-AD: 61

AD: 39

 NS IHC: n (%)
ERα ≥ 1% 0/59 (0) –
ERβ ≥ 1% 53/59 (90) –
PR ≥ 1% 0/59 (0) –
c-KIT ≥ 1% 0/59 (0) –
Gebert et al. [30]

37 patients

37 samples

32.7,

0.9–64.7

 74/26 100 E-AD and AD: 100

< 5: 10

> 5: 8

19 missing

 IHC: n (%)
β-catenin (n) > 20% 8/37 (22) –
β-catenin (n) 1–19% 17/37 (46) –
p53 ≥ 2% 12/37 (32) –
β-catenin (n) and p53 – p < 0.05d
MIB1 ≥ 2% 1/37 (3) –
EGFR ≥ 5% 0/37 (0) –
HER2 ≥ 5% 0/37 (0) –
c-Kit ≥ 5% 0/37 (0) –
Misemer et al. [51]

29 patients

29 samples

32,

10–80

 48/52 93

E-AD: 79

AD: 14

I-AD: 7

 NS Correlation (IHC staining with CDR): r (95% CI)
ADAM12 and log[CDR] 0.30 (0.25, 0.39) p < 0.001e
FAP-alpha and log[CDR] 0.44 (0.27, 0.60) p < 0.001e
WISP1 and log[CDR] 0.27 (0.10, 0.42) p < 0.001e
SOX11 and log[CDR] 0.14 (−0.09, 0.30) p = 0.24e
Ishizuka et al. [46]

27 patients

27 samples

37,

13–72

 70/30 100

E-AD: 78

AD: 22

 NS IHC: n (%)
ERα > 10% 2/27 (7.4) –
ERβ > 10% 2/27 (7.4) –
PR-A > 10% 7/27 (25.9) –
PR-B > 10% 9/27 (33.3) –
AR > 10% 14/27 (52.9) –
Leithner et al. [43]

80 patients

116 samples (26)

34,

0–83

 61/39 NS

E-AD: 58

AD: 26

I-AD: 13

 NS IHC (E-AD only): n (%)
ERα ≥ 10% 0/46 (0) –
ERβ ≥ 10% 4/46 (8.7) –
PR ≥ 10% 0/46 (0) –
AR > 5% 6/46 (13.0) –
Cathepsin D ≥ 10% 46/46 (100) –
c-Kit ≥ 10% 0/46 (0) –
Ki-67 > 5% 14/46 (30.4) –
HER2 > 1% 0/46 (0) –
Colombo et al. [49]

152 patients

195 samples (54)

 NS NS 100

E-AD: 87

I-AD: 13

 NS IHC: n (%)
ADAM12 195/195 (100) –
Midkine 90/195 (46) –
MMP2 189/195 (97) –
IHC: intensity score (%) [0 = none, 1 = low, 2 = moderate/strong]
ADAM12

1 (34)

2 (66)

 –
Midkine 0 (54) –
MMP2

1 (40)

2 (57)

 –
MT CTNNB1 and MMP2 intensity – p = 0.0438a
Ahlen et al. [50] DTF mRNA expression (in situ hybridisation): n (%)

7 patients

7 samples

40.1,

26–52

 71/29 NS E-AD: 100 NS DTF
EMMPRIN
BFT <10% 2/7 (28.6) –
6 patients 34, 50/50 NA E-AD: 100 NS 10–70% 1/7 (14.2) –
27–65 > 70% 3/7 (42.9) –
MMP2
<10% 2/7 (28.6) –
10–70% 0/7 (0) –
> 70% 4/7 (57.1) –
MMP14 <10% 4/7 (57.1) –
BFT
EMMPRIN > 70% 1/6 (17) –
MMP2 > 70% 0/6 (0) –
MMP14 > 70% 0/6 (0) –
DTF and BFT
EMMPRIN – p >  0.05a
MMP2 – p > 0.05a
MMP14 – p > 0.05a
Brautigam et al. [47]

69 patients

69 samples (19)

40†,

0–73

 39/61 90

E-AD and AD: 67

I-AD: 13

Unknown: 20

5.5‡,

0.7–30

 IHC (IRS > 0): n (%)
ERα (n) 0/42 (0) –
ERβ (n) 1/37 (2.7) –
ERβ (c) 18/33 (54.5) –
PR (n) 0/41 (0) –
AR (n) 1/33 (3.0) –
PARP1 (n) 57/58 (98.3) –
PARP1 (c) 0/58 (0) –
PARP1 (n) IRS 2-3 47/58 (81) –
Correlation: r
Ki-67 positivity and PARP-1 IRS −0.375 p = 0.041f
Saito et al. [31]

12 patients

17 samples (6)

32.6,

12–70

 53/47 100 E-AD: 100 NS Gene sequencing: n (%)
CTNNB1
S45F 5/17 –
T42R 1/17 –
mRNA expression: V (target protein mRNA value/house-keeping gene value)
MT CTNNB1 and CCND1 4259.60 p = 0.0120b
MT CTNNB1 and β-catenin 141.02 p = 0.0036b
IHC: n (%)
β-catenin (n) ≥ 80% 12/17 (70.6) –
β-catenin (n) 50–70% 5/17 (29.4) –
Mignemi et al. [32] DTF IHC: n (%)

27 patients

27 samples

26.6,

1–73

 52/48 100

E-AD: 78

AD: 11

Unknown:

11

5.8‡,

1–15

 β-catenin (n) > 5%
DTF 19/27 (70 *

p = 0.0003g

*p < 0.01h
HS 2/14 (14)*
FT 0/6 (0)*
HS p-SMAD2/3 > 5%
14 samples 43.3, 71/29 NA E-AD: 71 NS DTF 26/27 (96)*

p < 0.0001g

*p < 0.001h
17–58 AD: 29 HS 4/14 (29)*
FT FT 0/6 (0)*
6 samples

48.3,

34–57

 50/50 NA

E-AD: 33

AD: 67

 NS p-SMAD1/5/8 > 5%
DTF 5/27 (17) p >  0.005g
HS 2/14 (14)
FT 0/6 (0)
COX2
DTF 22/27 (83)*

p < 0.0001g

p < 0.01h
HS 3/14 (21)*
FT 0/6 (0)*
Correlation: p
β-catenin and COX2 0.034 p = 0.873f
TGFR1 and p-SMAD2/3 0.651 p = 0.0006f
COX2 and p-SMAD2/3 0.760 p < 0.0001f
COX2 and TGFR1 0.714 p = 0.0001f
Cates et al. [40] DTF IHC: n (%), median intensity score (0, 1 +, 2 +, 3 +)

27 patients

27 samples

26.6,

1–73

 52/48 100

E-AD: 78

AD: 11

Unknown: 11

5.5‡,

1–15

 PDGFRβ expression
DTF 27/27 (100), 3 +*

p < 0.001g

*p < 0.01h
HS 14/14 (100), 2 +
FT 5/6 (80) 2 +*
HS MET expression
14 samples NS NS NA NS NS DTF 24/27 (89), 1 +*

p = 0.0005g

*p < 0.001h
FT HS 14/14 (100), 1 +
6 samples NS NS NA NS NS FT 0/6 (0), 0*
EGFR expression
DTF 3/27 (12), 0 p >  0.005g
HS 0/14 (0), 0
FT 0/6 (0), 0
p-Akt expression
DTF 15/27 (56), 1 +*

p = 0.0002g

*p < 0.01h
HS NS, 2 +*
FT 2/6 (33), 0
Varghese et al. [33] DTF IHC: n (%), staining intensity (1 +, weak; 2 +, moderate; 3 +, strong)

15 patients

15 samples

35.2,

22–62

 40/60 NS

E-AD: 73

AD: 27

 NS β-catenin (n)
DTF 15/15 (100), 2 + to 3 + –
STDC STDC 0/10 (0) –
10 samples NS NS NA NS NS TGFβ (c)
DTF 15/15 (100), 2 + to 3 + –
STDC

8/10 (80), 2 + to 3 +

2/10 (20), 1 +

 –
CTGF (c)
DTF

10/15 (66.7), 2 + to 3 +

5/15 (33), 1 +

 –
STDC

4/10 (40), 2  + to 3  +

6/10 (60), 1  +

 –

AD abdominal, AI apoptotic index, AR androgen receptor, BFT benign fibrous tumour, CDR chromosome density ratio, CI confidence interval, COX2 cyclooxygenase-2, CTGF connective tissue growth factor, DTF desmoid-type fibromatosis, E-AD extra-abdominal, EGFR epidermal growth factor receptor, EMMPRIN extracellular matrix metalloproteinase inducer, ERα oestrogen receptor-α, ERβ oestrogen receptor-β, FAP-alpha fibroblast activation protein-alpha, FT fibrous tissue, HER2 human epidermal growth factor receptor 2, HS hypertrophic scar, I-AD intra-abdominal, IHC immunohistochemistry, IRS immunoreactive score (staining intensity multiplied by percentage of positive tumour cells), LI labelling index (percent of positive immunostaining tumour cells), MCM5 minichromosome maintenance complex component 5, MMP matrix metalloproteinase, MT mutated, MVD microvessel density (mm2), n number of cases, NA not applicable, NS not specified, p Spearman’s correlation coefficient, PARP1 poly(ADP-ribose) polymerase 1, PCNA proliferating cell nuclear antigen, PDGFRα platelet-derived growth factor receptor-α, PDGFRβ platelet-derived growth factor receptor-β, PR-A progesterone receptor-A, PR-B progesterone receptor-B, r Pearson’s correlation coefficient, SD standard deviation, SOX11 SRY-box transcription factor 11, STDC scar tissue and normal dermal collagen, S45F serine to phenylalanine substitution in codon 45, S45P serine to proline substitution in codon 45, T41A threonine to alanine substitution in codon 41, T41I threonine to isoleucine substitution in codon 41, T42R threonine to arginine substitution in codon 42, TGFβ transforming growth factor-β, VEGF vascular endothelial growth factor, WISP1 Wnt inducible signalling pathway protein 1, WT wild-type, (c) cytoplasmic staining, (c + n) cytoplasmic and nuclear staining, (n) nuclear staining, (+) positive, (–) negative

†Indicates median age (years)

‡Indicates median tumour size (cm).

aFisher’s exact test

bMann–Whitney U test

cStudent’s t test

dχ2 test

ePearson’s correlation

fSpearman’s correlation

gKruskal–Wallis test

hDunn’s multiple comparison test

Significant p values indicated in bold