Table 1.
Clinicopathological characteristics of breast cancer
| Variables | N | % | |
|---|---|---|---|
| Side | left | 66 | 44.9 |
| right | 81 | 55.1 | |
| Histological type | lobular | 18 | 12.4 |
| ductal | 123 | 84.8 | |
| other | 4 | 2.8 | |
| Histological grade | HG1 | 17 | 11.9 |
| HG2 | 73 | 51 | |
| HG3 | 53 | 37.1 | |
| Nuclear grade | NG1 | 17 | 15.2 |
| NG2 | 64 | 57.1 | |
| NG3 | 31 | 27.7 | |
| Mitotic index | grade 1 | 19 | 42.2 |
| grade 2 | 20 | 44.4 | |
| grade 3 | 6 | 13.3 | |
| Tumor necrosis | absent | 26 | 21.7 |
| present | 94 | 78.3 | |
| Desmoplasia | low | 17 | 16.3 |
| medium | 55 | 52.9 | |
| high | 32 | 30.8 | |
| Periductal elastosis | low | 19 | 20.0 |
| medium | 20 | 44.4 | |
| high | 16 | 35.6 | |
| Perineural invasion | absent | 101 | 68.7 |
| present | 46 | 31.3 | |
| Lymphatic invasion | absent | 72 | 48.9 |
| present | 75 | 51.1 | |
| Vascular invasion | absent | 113 | 76.9 |
| present | 34 | 23.1 | |
| HER2 | negative | 115 | 79.3 |
| positive | 30 | 20.7 | |
| Ki67 | low | 30 | 20..9 |
| medium | 42 | 29.4 | |
| high | 71 | 49.7 | |
| Molecular subtypes | Lum A | 30 | 20.4 |
| Lum B | 76 | 51.7 | |
| HER2 + | 19 | 12.9 | |
| TNBC | 22 | 15 | |
| T status | T1 | 48 | 35.8 |
| T2 | 64 | 47.8 | |
| T3 | 9 | 6.7 | |
| T4 | 13 | 9.7 | |
| N status | N0 | 50 | 37.3 |
| N1 | 48 | 35.8 | |
| N2 | 19 | 14.2 | |
| N3 | 17 | 12.7 | |
Figure 1.
Expression of p21 in relation to cytological changes in the epithelium. A.
A statistically significant difference was observed between each of the mentioned groups except between the ISC and AH groups (Mann Whitney U, p=0.06). The result is shown as the median. Microscopic image of p21 expression in various histo and cytomorphological changes: B. IBC. C. ISC. D. AH. E. NE (immunohistochemical analysis, original magnification 200x).
Figure 2.
Correlation of p21 expression between groups in relation to cytological changes in the epithelium (Spearman ρ).
A strong positive correlation was found between all groups: A. IBC and ISC (p<0.001, ρ=0.709), B. IBC and AH (p<0.001, ρ=0.726), C. IBC and NE (p<0.001, ρ=0.701), D. ISC and AH (p<0.001, ρ=0.833), E. ISC and NE (p<0.001, ρ=0.798) and F. AH and NE (p<0.001, ρ=0.905).
Figure 3.
Expression of p21 in different molecular subtypes of IBC.
A statistically significant difference was shown between the following groups: Lum A and Lum B (Mann-Whitney U, p=0.021), Lum A and HER2 (Mann-Whitney U, p<0.00), Lum B and HER2 (Mann-Whitney U, p=0.048), HER2 and TNBC (Mann-Whitney U, p=0.006). The result is presented as median.
Figure 4.
p21 expression depending on Ki67 expression and HER2 expression.
A. p21 expression in tumor cells depends on Ki67 expression. The result is shown as the median (Kruskal-Wallis, p=0.019). B. There is a significant difference in p21 expression depending on HER2 expression. The result is shown as the median (Mann Whitney U, p=0.001).
Figure 5.
Expression of p21 depending on expression of nuclear grade and T status.
Expression of p21 in tumor cells depends on A. nuclear grade (Kruskal-Wallis, p=0.026) and B. T status (Kruskal-Wallis, p=0.05). The result is shown as the median.
Figure 6.
Expression of p21 depending on the expression of ER and PR.
The expression of ER and PR was analyzed through the Allred score. The increase in p21 expression in tumor cells was accompanied by a statistically significantly reduced expression of A. ER (p=0.015, ρ=−0.225) and B. PR (p=0.027, ρ=−0.205) (small negative correlation).
Figure 7.
ROC curve of p21 expression in NIL and IBC.
The calculated value of AUC=0.712 with a sensitivity of 64.4% and a specificity of 64.4% determined a threshold value of 7.5%.
Figure 8.
A. Frequency of p21+ and p21− IBC in relation to the treshold value of p21 expression.
Microscopic image of p21 expression in relation to the threshold value: B. p21+ and C. p21− (immunohistochemical analysis, original magnification 200x).
Table 2.
Association between p21 expression in IBC and examined clinicopathological characteristics.
| Variables | p21 cut off 7.5% | Chi-Square | p | ||
|---|---|---|---|---|---|
| − | + | ||||
| Mononuclear infiltrate | absent | 1 (9.1%) | 3 (5.8%) | 0.666 | 0.881 |
| low | 4 (36.4%) | 20 (38.5%) | |||
| medium | 5 (45.5%) | 20 (38.5%) | |||
| high | 1 (9.1%) | 9 (17.3%) | |||
| Histological type | lobular | 1 (6.7%) | 5 (6.7%) | 0.622 | 0.733 |
| ductal | 14 (93.3) | 67 (89.3) | |||
| other | 0 (0.0%) | 3 (4.0%) | |||
| Histological grade | HG1 | 2 (12.5%) | 8 (11.0%) | 0.364 | 0.834 |
| HG2 | 7 (43.8%) | 38 (52.1%) | |||
| HG3 | 7 (43.8%) | 27 (37.0) | |||
| Nuclear grade | NG1 | 0 (0.0%) | 6 (9.7%) | 2.096 | 0.351 |
| NG2 | 7 (53.8%) | 37 (59.7%) | |||
| NG3 | 6 (46.2%) | 19 (30.6%) | |||
| Tumor necrosis | absent | 2 (15.4%) | 17 (27.0%) | 0.278 | 0.598 |
| present | 11 (84.6%) | 46 (73.0%) | |||
| Perineural invasion | absent | 13 (81.3%) | 49 (64.5%) | 1.015 | 0.314 |
| present | 3 (18.8) | 27 (35.5%) | |||
| Lymphatic invasion | absent | 5 (31.3%) | 37 (48.7%) | 0.993 | 0.319 |
| present | 11 (68.8%) | 39 (51.3%) | |||
| Vascular invasion | absent | 12 (75.0%) | 57 (75.0%) | 0.000 | 1.000 |
| present | 4 (25.0%) | 19 (25.0%) | |||
| Molecular subtypes | Lum A | 1 (6.3%) | 10 (13.2%) | 11.490 | 0.009 |
| Lum B | 8 (50.0%) | 42 (55.3%) | |||
| HER2 + | 0 (0.0%) | 15 (19.7%) | |||
| TNBC | 7 (43.8%) | 9 (11.8%) | |||
| HER2 | negative | 16 (100.0%) | 49 (66.2%) | 5.895 | 0.015 |
| positive | 0 (0.0%) | 25 (33.8%) | |||
| Ki67 | low | 2 (13.3%) | 10 (13.5%) | 1.075 | 0.584 |
| medium | 6 (40.0%) | 20 (27.0%) | |||
| high | 7 (46.7%) | 44 (59.5) | |||
| T status | T1 | 3 (20.0%) | 22 (32.4%) | 2.924 | 0.404 |
| T2 | 9 (60.0%) | 34 (50.0%) | |||
| T3 | 2 (13.3%) | 3 (4.4%) | |||
| T4 | 1 (6.7%) | 9 (13.2%) | |||
| N status | N0 | 4 (26.7%) | 23 (33.3%) | 1.504 | 0.681 |
| N1 | 8 (53.3%) | 26 (37.7%) | |||
| N2 | 1 (6.7%) | 10 (14.5%) | |||
| N3 | 2 (13.3%) | 10 (14.5%) | |||