Growth Factors and Stromal Matrix Proteins Associated with Mammographic Densities

DOI: Published March 2001

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Fig. 1.
Image analysis. Top, negative control for IGF-I staining; middle, IGF-I staining; bottom, IGF-I-stained area outlined in red by thresholding. All of the images are shown at ×40 magnification.
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Fig. 2.
Measurement of the selection of fields. Illustration of the method used to select fields to be measured. Eighty fields in each section were randomly selected along the track starting from the top of the section. Every second or third field on the track was selected so that the entire section could be covered by these eighty fields.

Table 1

Selected characteristics of subjects

	Low density (n = 46)	High density (n = 46)
Median age	48.5	49.0
Interquartile range	(45–55)	(45–55)
Radiological classification (No. of subjects)
0% density	7	0
>0–<10% density	24	0
10–25% density	14	0
25–50% density	0	1
50–75% density	0	7
>75% density	0	38
Missing	1	0
Histological classification (No. of subjects)
Normal	10	1
Stromal fibrosis	4	5
Nonproliferative, fibrocystic change	23	17
Proliferative FCC^a without atypia	8	21
Proliferative FCC with atypia	0	1
Not assessed/missing	1 (fibroadenoma)	1 (missing)

Table 2

Comparison of molecular factors in tissue from breasts with low density and high density (n = 46 age matched pairs)

	Low density^a	High density^a	Difference (low-high)^b	P^c
Percentage of nuclear area (n = 46)	0.27^a (0.89)	0.85 (0.91)	−0.58 (1.40)	0.007
Percentage of total collagen^d (n = 41)	2.21 (1.66)	3.32 (1.56)	−1.11 (2.27)	0.003
Percentage of IGF-1^e (n = 45)	−0.29 (1.82)	0.48 (1.37)	−0.77 (2.15)	0.02
Percentage of TGF-α^e (n = 45)	−1.36 (2.05)	−1.49 (2.24)	0.12 (2.87)	0.77
Percentage of TIMP-3 (n = 46)	−0.99 (2.47)	−0.12 (2.49)	−0.86 (3.27)	0.08

^a Results expressed as mean (SD) of log-transformed values.
^b Paired differences (low-high density log-transformed value) expressed as mean (SD).
^c P for t-test for paired difference.
^d Values missing because of sections unsuitable for staining (n = 2) and staining measurement problems (n = 2).
^e Value missing because of sections unsuitable for staining (n = 1 for each measure).

Table 3

Comparison of molecular factors in tissue from breasts with low and high breast density in women < and ≥ 50 years of age

	Low density^a	High density^a	Difference (low-high)^b	P^c
A. Women <50 years of age; n = 24 pairs; mean age = 44 years
Percentage of nuclear area	0.07^a (0.84)	1.23 (0.80)	−1.17 (1.16)	0.0001
Percentage of total collagen (n = 22)	1.76 (1.86)	3.17 (1.83)	−1.41 (2.64)	0.02
Percentage of IGF-1	−0.42 (1.42)	0.89 (1.05)	−1.31 (1.69)	0.0009
Percentage of TGF-α	−1.53 (1.81)	−1.34 (2.49)	−0.19 (2.95)	0.75
Percentage of TIMP-3	−1.54 (2.21)	0.52 (2.22)	−2.06 (3.17)	0.004
B. Women ≥50 years of age; n = 22 age matched pairs; mean age = 57 years
Percentage of nuclear area	0.49 (0.91)	0.42 (0.85)	0.07 (1.36)	0.82
Percentage of total collagen (n = 19)	2.80 (1.24)	3.32 (0.96)	−0.76 (1.77)	0.08
Percentage of IGF-1 (n = 21)	−0.14 (2.22)	0.02 (1.57)	−0.16 (2.48)	0.78
Percentage of TGF-α (n = 21)	−1.17 (2.32)	−1.65 (1.95)	0.49 (2.81)	0.44
Percentage of TIMP-3	−0.38 (2.65)	−0.83 (2.63)	0.45 (2.90)	0.48

^a Results expressed as mean (SD) of log-transformed values.
^b Paired difference (low-high density log-transformed value) expressed as mean (SD).
^c P for t test for paired difference.

Table 4

Comparison of molecular factors in tissue from biopsies taken from fatty and dense sites (unpaired)

	Fatty tissue at biopsy site	Dense tissue at biopsy site	P^a
Percentage of nuclear area	1.01 (0.54–2.33)^b	2.52 (1.06–5.00)	0.0004
	0.17 ^c	0.87
	n = 40	n = 51
Percentage of total collagen	11.69 (3.49–33.48)	35.54 (10.98–62.70)	0.002
	2.14	3.02
	n = 35	n = 48
Percentage of IGF-1	1.13 (0.21–2.64)	1.94 (0.75–4.06)	0.05
	−0.32	0.44
	n = 40	n = 50
Percentage of TGF-α	0.30 (0.06–0.81)	0.42 (0.11–1.32)	0.30
	−1.70	−1.21
	n = 39	n = 51
Percentage of TIMP-3	0.45 (0.05–3.63)	0.54 (0.06–5.93)	0.45
	−0.81	−0.39
	n = 40	n = 51

^a P for two sample Wilcoxon tests comparing median values.
^b Median (interquartile range) of untransformed values.
^c Mean of log-transformed data in italics to allow comparison with Tables 2<$REFLINK> and 3<$REFLINK> .