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

Miha Koren

Miha Koren

Institute of Pathology, Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
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Koren, Miha
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Margareta Zlajpah

Margareta Zlajpah

Institute of Pathology, Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
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Zlajpah, Margareta
, 
Mario Poljak

Mario Poljak

Institute of Microbiology and Immunology, Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
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Poljak, Mario
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Kristina Fujs Komlos

Kristina Fujs Komlos

Institute of Microbiology and Immunology, Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
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Komlos, Kristina Fujs
 and 
Margareta Strojan Flezar

Margareta Strojan Flezar

Institute of Pathology, Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
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Flezar, Margareta Strojan
  
Apr 24, 2025
Expression of the stem cell markers NANOG and SOX2 in the cervical squamous carcinogenesis's Cover Image
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Article Category: research article
Published Online: Apr 24, 2025
Page range: 213 - 224
Received: Mar 05, 2025
Accepted: Mar 26, 2025
DOI: https://doi.org/10.2478/raon-2025-0026
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© 2025 Miha Koren et al., published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.

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
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

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

NANOG SIxP score, a ± SD p-value1 SOX2 SIxP score, a ± SD p-value1
C (LSIL) LSIL C (LSIL) LSIL
2.30 ± 0.95 7.50 ± 2.46 0.000 3.00 ± 1.41 5.40 ± 2.63 0.054
C (HSIL/CIN 2) HSIL/CIN 2 C (HSIL/CIN 2) HSIL/CIN 2
3.30 ± 2.06 9.20 ± 3.79 0.002 2.20 ± 1.48 7.70 ± 2.75 0.000
C (HSIL/CIN 3) HSIL/CIN 3 C (HSIL/CIN 3) HSIL/CIN 3
2.00 ± 0.94 10.40 ± 2.07 0.000 2.30 ± 1.16 10.10 ± 3.84 0.002
C (CSCC) CSCC C (CSCC) CSCC
1.44 ± 1,01 11.56 ± 1.33 0.000 2.44 ± 0,53 10.22 ± 2.73 0.000
C (HSIL) HSIL C (HSIL) HSIL
2.65 ± 1.65 9.80 ± 2.96 0.000 2.25 ± 1.26 8.90 ± 3.39 0.000

Comparison of NANOG and SOX2 staining between squamous lesions

NANOG SIxP score, a ± SD p-value1 SOX2 SIxP score, a ± SD p-value1
LSIL HSIL/CIN 2 LSIL HSIL/CIN 2
7.50 ± 2.46 9.20 ± 3.79 0.101 5.40 ± 2.63 7.70 ± 2.75 0.114
HSIL/CIN 2 HSIL/CIN 3 HSIL/CIN 2 HSIL/CIN 3
9.20 ± 3.79 10.40 ± 2.07 0.547 7.70 ± 2.75 10.10 ± 3.84 0.031
HSIL/CIN 3 CSCC HSIL/CIN 3 CSCC
10.40 ± 2.07 11.56 ± 1.33 0.165 10.10 ± 3.84 10.22 ± 2.73 0.805
LSIL HSIL LSIL HSIL
7.50 ± 2.46 9.80 ± 2.96 0.018 5.40 ± 2.63 8.90 ± 3.39 0.009
HSIL CSCC HSIL CSCC
9.80 ± 2.96 11.56 ± 1.33 0.078 8.90 ± 3.39 10.22 ± 2.73 0.370

Results of human papillomavirus (HPV) genotyping in squamous lesions

HPV type HPV 16 HPV 18 HPV 31 HPV 39 HPV 51 HPV 52 HPV 53 HPV 56 HPV 58 HPV 59 HPV 68 HPV 66 HPV 70 HPV 42
LSIL, n 4 0 0 3 2 0 3 1 0 1 2 5 2 2
HSIL/CIN 2, n 4 1 1 0 1 2 0 1 2 0 0 1 0 0
HSIL/CIN 3, n 8 0 3 0 0 0 1 0 0 1 0 0 0 0
CSCC, n 6 2 2 0 3 0 0 0 0 0 0 0 1 0

Evaluation of SOX2 staining in controls and squamous lesions

SOX2 SI, n (%) SOX2 P, n (%) SOX2 T, n (%)
Score 0 1 2 3 0 1 2 3 4 0 1 2 3
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

Evaluation of NANOG staining in controls and squamous lesions

NANOG SI, n (%) NANOG P, n (%) NANOG T, n (%)
Score 0 1 2 3 0 1 2 3 4 0 1 2 3
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
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