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Prognostic Significance of P21 Protein in Breast Cancer Cover

Prognostic Significance of P21 Protein in Breast Cancer

EABR. Experimental and Applied Biomedical Research
Volume 26 (2025): Issue 3 (September 2025)
By: Dalibor Jovanovic,  Slobodanka Mitrovic,  Dzemila Alic,  Danijela Besic,  Dragan Knezevic,  Jelena Dimitrijevic and  Milena Ilic  
Open Access
|Feb 2026

Figures & Tables

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).
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).
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.
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).
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.
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).
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%.
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).
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).

Clinicopathological characteristics of breast cancer

VariablesN%
Sideleft6644.9
right8155.1
Histological typelobular1812.4
ductal12384.8
other42.8
Histological gradeHG11711.9
HG27351
HG35337.1
Nuclear gradeNG11715.2
NG26457.1
NG33127.7
Mitotic indexgrade 11942.2
grade 22044.4
grade 3613.3
Tumor necrosisabsent2621.7
present9478.3
Desmoplasialow1716.3
medium5552.9
high3230.8
Periductal elastosislow1920.0
medium2044.4
high1635.6
Perineural invasionabsent10168.7
present4631.3
Lymphatic invasionabsent7248.9
present7551.1
Vascular invasionabsent11376.9
present3423.1
HER2negative11579.3
positive3020.7
Ki67low3020..9
medium4229.4
high7149.7
Molecular subtypesLum A3020.4
Lum B7651.7
HER2 +1912.9
TNBC2215
T statusT14835.8
T26447.8
T396.7
T4139.7
N statusN05037.3
N14835.8
N21914.2
N31712.7

Association between p21 expression in IBC and examined clinicopathological characteristics_

Variablesp21 cut off 7.5%Chi-Squarep
−+
Mononuclear infiltrateabsent1 (9.1%)3 (5.8%)0.6660.881
low4 (36.4%)20 (38.5%)
medium5 (45.5%)20 (38.5%)
high1 (9.1%)9 (17.3%)
Histological typelobular1 (6.7%)5 (6.7%)0.6220.733
ductal14 (93.3)67 (89.3)
other0 (0.0%)3 (4.0%)
Histological gradeHG12 (12.5%)8 (11.0%)0.3640.834
HG27 (43.8%)38 (52.1%)
HG37 (43.8%)27 (37.0)
Nuclear gradeNG10 (0.0%)6 (9.7%)2.0960.351
NG27 (53.8%)37 (59.7%)
NG36 (46.2%)19 (30.6%)
Tumor necrosisabsent2 (15.4%)17 (27.0%)0.2780.598
present11 (84.6%)46 (73.0%)
Perineural invasionabsent13 (81.3%)49 (64.5%)1.0150.314
present3 (18.8)27 (35.5%)
Lymphatic invasionabsent5 (31.3%)37 (48.7%)0.9930.319
present11 (68.8%)39 (51.3%)
Vascular invasionabsent12 (75.0%)57 (75.0%)0.0001.000
present4 (25.0%)19 (25.0%)
Molecular subtypesLum A1 (6.3%)10 (13.2%)11.4900.009
Lum B8 (50.0%)42 (55.3%)
HER2 +0 (0.0%)15 (19.7%)
TNBC7 (43.8%)9 (11.8%)
HER2negative16 (100.0%)49 (66.2%)5.8950.015
positive0 (0.0%)25 (33.8%)
Ki67low2 (13.3%)10 (13.5%)1.0750.584
medium6 (40.0%)20 (27.0%)
high7 (46.7%)44 (59.5)
T statusT13 (20.0%)22 (32.4%)2.9240.404
T29 (60.0%)34 (50.0%)
T32 (13.3%)3 (4.4%)
T41 (6.7%)9 (13.2%)
N statusN04 (26.7%)23 (33.3%)1.5040.681
N18 (53.3%)26 (37.7%)
N21 (6.7%)10 (14.5%)
N32 (13.3%)10 (14.5%)
DOI: https://doi.org/10.2478/sjecr-2023-0005 | Journal eISSN: 2956-2090 | Journal ISSN: 2956-0454
Journal RSS Feed
Language: English
Page range: 275 - 286
Submitted on: Mar 28, 2023
|
Accepted on: Apr 13, 2023
|
Published on: Feb 23, 2026
Published by: University of Kragujevac, Faculty of Medical Sciences
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
Cyclin-Dependent Kinase Inhibitor p21,
breast cancer,
molecular subtype,
immunohistochemistry
Related subjects:
Medicine,
Clinical medicine,
Clinical medicine, other

© 2026 Dalibor Jovanovic, Slobodanka Mitrovic, Dzemila Alic, Danijela Besic, Dragan Knezevic, Jelena Dimitrijevic, Milena Ilic, published by University of Kragujevac, Faculty of Medical Sciences
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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