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Expression of the stem cell markers NANOG and SOX2 in the cervical squamous carcinogenesis Cover

Expression of the stem cell markers NANOG and SOX2 in the cervical squamous carcinogenesis

Radiology and Oncology
Volume 59 (2025): Issue 2 (June 2025)
By: ,  ,  ,   and    
Open Access
|Apr 2025
Figures & tables

Figures & Tables

TABLE 1.

Results of human papillomavirus (HPV) genotyping in squamous lesions

HPV typeHPV 16HPV 18HPV 31HPV 39HPV 51HPV 52HPV 53HPV 56HPV 58HPV 59HPV 68HPV 66HPV 70HPV 42
LSIL, n40032031012522
HSIL/CIN 2, n41101201200100
HSIL/CIN 3, n80300010010000
CSCC, n62203000000010

1 CSCC = cervical squamous cell carcinoma; HPV = human papillomavirus; HSIL/CIN 2 = high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2; HSIL/CIN 3 = high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 3; LSIL = low-grade squamous intraepithelial lesion; n = number of cases

Figure 1.

Representative images of p16 (b, g, l, q, v), Ki-67 (c, h, m r, w), NANOG (d, i, n, s, x) and SOX2 (e, j, o, t, y) immunohistochemical staining in a control (a-e), low-grade squamous intraepithelial lesion (LSIL) (f-j), high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2 (HSIL/CIN 2) (k-o), high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 3 (HSIL/CIN 3) (p-t) and cervical squamous cell carcinoma (CSCC) (u-y).

HE = haematoxylin and eosin stain

TABLE 2.

Evaluation of NANOG staining in controls and squamous lesions

NANOG SI, n (%)NANOG P, n (%)NANOG T, n (%)
Score0123012340123
Controls (n = 40)3 (7.5)32 (80)5 (12.5)0 (0)3 (7.5)6 (15)22 (55)8 (20)1 (2.5)3 (7.5)4 (10)28 (70)5 (12.5)
LSIL (n = 10)0 (0)2 (20)7 (70)1 (10)0 (0)0 (0)0 (0)1 (10)9 (90)0 (0)0 (0)0 (0)10 (100)
HSIL/CIN 2 (n = 10)1 (10)0 (0)4 (40)5 (50)1 (10)0 (0)0 (0)0 (0)9 (90)1 (0)0 (0)0 (0)9 (90)
HSIL/CIN 3 (n = 10)0 (0)0 (0)1 (10)9 (90)0 (0)0 (0)0 (0)0 (0)10 (10)0 (0)0 (0)0 (0)10 (100)
CSCC (n = 10)0 (0)0 (0)1 (10)9 (90)0 (0)0 (0)0 (0)0 (0)10 (100)Not applicable1

1 CSCC = cervical squamous cell carcinoma; HSIL/CIN 2 = high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2; HSIL/CIN 3 = high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 3; LSIL = low-grade squamous intraepithelial lesion; n = number of cases; P = percentage of positive cells; SI = staining intensity for NANOG; T = thickness of staining; % = percentage of all cases in each category

11 T was not evaluated in CSCC.

TABLE 3.

Evaluation of SOX2 staining in controls and squamous lesions

SOX2 SI, n (%)SOX2 P, n (%)SOX2 T, n (%)
Score0123012340123
Controls (n = 40)2 (5)33 (82.5)5 (12.5)0 (0)2 (5)1 (2.5)26 (65)10 (25)0 (0)2 (5)1 (2.5)31 (77.5)6 (15)
LSIL (n = 10)0 (0)4 (40)6 (60)0 (0)0 (0)0 (0)2 (20)4 (40)4 (40)0 (0)0 (0)4 (40)6 (60)
HSIL/CIN 2 (n = 10)0 (0)1 (10)7 (70)2 (20)0 (0)0 (0)0 (0)4 (40)6 (60)0 (0)0 (0)1 (10)9 (90)
HSIL/CIN 3 (n = 10)0 (0)1 (10)1 (10)8 (80)1 (10)0 (0)0 (0)1 (10)8 (80)0 (0)0 (0)0 (0)10 (100)
CSCC (n = 10)0 (0)0 (0)3 (30)7 (70)0 (0)0 (0)0 (0)2 (20)8 (80)Not applicable1

1 CSCC = cervical squamous cell carcinoma; HSIL/CIN 2 = high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2; HSIL/CIN 3 = high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 3; LSIL = low-grade squamous intraepithelial lesion; n = number of cases; P = percentage of positive cells; SI = staining intensity for NANOG; T = thickness of staining; % = percentage of all cases in each category

11 T was not evaluated in CSCC.

TABLE 4.

Comparison of NANOG and SOX2 staining between squamous lesions and their adjacent control non-dysplastic squamous epithelium

NANOG SIxP score, a ± SDp-value1SOX2 SIxP score, a ± SDp-value1
C (LSIL)LSILC (LSIL)LSIL
2.30 ± 0.957.50 ± 2.460.0003.00 ± 1.415.40 ± 2.630.054
C (HSIL/CIN 2)HSIL/CIN 2C (HSIL/CIN 2)HSIL/CIN 2
3.30 ± 2.069.20 ± 3.790.0022.20 ± 1.487.70 ± 2.750.000
C (HSIL/CIN 3)HSIL/CIN 3C (HSIL/CIN 3)HSIL/CIN 3
2.00 ± 0.9410.40 ± 2.070.0002.30 ± 1.1610.10 ± 3.840.002
C (CSCC)CSCCC (CSCC)CSCC
1.44 ± 1,0111.56 ± 1.330.0002.44 ± 0,5310.22 ± 2.730.000
C (HSIL)HSILC (HSIL)HSIL
2.65 ± 1.659.80 ± 2.960.0002.25 ± 1.268.90 ± 3.390.000
NANOG SIxT score2 a ± SDp-value1SOX2 SIxT score2, a ± SDp-value1
C (LSIL)LSILC (LSIL)LSIL
1.90 ± 0.325.70 ± 1.700.0002.50 ± 0.854.30 ± 1.890.0027
C (HSIL/CIN 2)HSIL/CIN 2C (HSIL/CIN 2)HSIL/CIN 2
3.00 ± 1.766.90 ± 2.850.0051.90 ± 0.996.10 ± 1.850.000
C (HSIL/CIN 3)HSIL/CIN 3C (HSIL/CIN 3)HSIL/CIN 3
2.20 ± 1.487.80 ± 1.550.0002.40 ± 1.178.10 ± 2.020.000
C (HSIL)HSILC (HSIL)HSIL
2.60 ± 1.597.35 ± 2.220.0002.15 ± 1.067.10 ± 2.100.000

1 a = average; C (HSIL) = control non-dysplastic squamous epithelium adjacent to high-grade squamous intraepithelial lesion; C (LSIL) = control non-dysplastic squamous epithelium adjacent to low-grade squamous intraepithelial lesion; C (HSIL/CIN 2) = control non-dysplastic squamous epithelium adjacent to high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2; C (HSIL/CIN 3) = control non-dysplastic squamous epithelium adjacent to high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 3; CSCC = cervical squamous cell carcinoma; C (CSCC) = control non-dysplastic squamous epithelium adjacent to cervical squamous cell carcinoma; HSIL = high-grade squamous intraepithelial lesion; HSIL/CIN 2 = high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2; HSIL/CIN 3 = high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 3; LSIL = low-grade squamous intraepithelial lesion; SD = standard deviation; SIxP score = staining intensity (SI) multiplied by percentage of positive cells (P); SIxT score = staining intensity (SI) multiplied by thickness of staining (T)

11 Comparisons between groups were tested by the Mann-Whitney test.

12 SIxT score was not calculated for CSCC because T was not evaluated in CSCC.

TABLE 5.

Comparison of NANOG and SOX2 staining between squamous lesions

NANOG SIxP score, a ± SDp-value1SOX2 SIxP score, a ± SDp-value1
LSILHSIL/CIN 2LSILHSIL/CIN 2
7.50 ± 2.469.20 ± 3.790.1015.40 ± 2.637.70 ± 2.750.114
HSIL/CIN 2HSIL/CIN 3HSIL/CIN 2HSIL/CIN 3
9.20 ± 3.7910.40 ± 2.070.5477.70 ± 2.7510.10 ± 3.840.031
HSIL/CIN 3CSCCHSIL/CIN 3CSCC
10.40 ± 2.0711.56 ± 1.330.16510.10 ± 3.8410.22 ± 2.730.805
LSILHSILLSILHSIL
7.50 ± 2.469.80 ± 2.960.0185.40 ± 2.638.90 ± 3.390.009
HSILCSCCHSILCSCC
9.80 ± 2.9611.56 ± 1.330.0788.90 ± 3.3910.22 ± 2.730.370
NANOG SIxT score2 a ± SDp-value1SOX2 SIxT score2, a ± SDp-value1
LSILHSIL/CIN 2LSILHSIL/CIN 2
5.70 ± 1.706.90 ± 2.850.1014.30 ± 1.896.10 ± 1.850.056
HSIL/CIN 2HSIL/CIN 3HSIL/CIN 2HSIL/CIN 3
6.90 ± 2.857.80 ± 1.550.5476.10 ± 1.858.10 ± 2.020.023
LSILHSILLSILHSIL
5.70 ± 1.707.35 ± 2.220.0184.30 ± 1.897.10 ± 2.100.003

1 a = average; CSCC = cervical squamous cell carcinoma; HSIL = high-grade squamous intraepithelial lesion; HSIL/CIN 2 = high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2; HSIL/CIN 3 = high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 3; LSIL = low-grade squamous intraepithelial lesion; SD = standard deviation; SIxP score = staining intensity (SI) multiplied by percentage of positive cells (P); SIxT score = staining intensity (SI) multiplied by thickness of staining (T)

11 Comparisons between groups were tested by the Mann-Whitney test.

12 SIxT score was not calculated for CSCC because T was not evaluated in CSCC.

DOI: https://doi.org/10.2478/raon-2025-0026 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099
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Language: English
Page range: 213 - 224
Submitted on: Mar 5, 2025
Accepted on: Mar 26, 2025
Published on: Apr 24, 2025
Published by: Association of Radiology and Oncology
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
cervical cancer,
cervical intraepithelial neoplasia,
squamous intraepithelial lesion,
cancer stem cell,
NANOG,
SOX2
Related subjects:
Medicine,
Clinical medicine,
Radiology

© 2025 Miha Koren, Margareta Zlajpah, Mario Poljak, Kristina Fujs Komlos, Margareta Strojan Flezar, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution 4.0 License.

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