Heterogeneity of GYPC Methylation and p16/Ki67 Immunostaining in Cervical Intraepithelial Neoplasia: Implications for Risk Stratification.
- 1Department of Pathology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, 410004, People's Republic of China.
Abstract
Background
GYPC methylation (GYPCm )is an early event in cancer transformation, whereas p16 and Ki67 are critical markers in cervical lesion pathology. This study aimed to explore the relationship between GYPCm status and the immunohistochemical markers p16, Ki67, and the combined immunostaining score (IS) in cervical lesions.Methods
A retrospective analysis was conducted on 203 histologically confirmed cervical lesion specimens collected from October 2022 to July 2023. The specimens included 79 cases of cervical intraepithelial neoplasia (CIN) grade 1 (CIN1) (38.9%), 48 cases of CIN2 (23.6%), 66 cases of CIN3 (32.5%), and 10 cases of cervical squamous cell carcinoma (SCC; 4.9%). Immunohistochemical staining for p16 and Ki67, as well as GYPCm testing, was performed. The association between GYPCm and IS was assessed.Results
GYPCm ΔCp decreased with increasing severity of cervical lesions (Cuzick trend test, P < 0.001). p16, Ki67, and IS showed an increasing trend with the severity of cervical lesions (all P trend < 0.001). Moreover, GYPCm increased with p16, Ki67, and IS (all P trend < 0.001). An IS of 5-6 and high GYPCm were observed in all SCC cases. Heterogeneity of GYPCm and IS was present in CIN: in CIN1, 15 cases had an IS of 3-4 with a moderate or high GYPCm . In CIN2, seven cases had an IS of 3-4 with low GYPCm .Conclusion
Significant heterogeneity in IS and GYPCm exists in CIN. These findings suggest that GYPCm combined with p16/Ki67 immunostaining may be useful for risk stratification of cervical lesions. However, because this was a retrospective cross-sectional study without longitudinal follow-up, the value of these markers in predicting short-term cancer progression requires prospective validation before they can be used to guide personalized management.
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BibTeX
@article{lian2026heterogeneity,
title = {{Heterogeneity of GYPC Methylation and p16/Ki67 Immunostaining in Cervical Intraepithelial Neoplasia: Implications for Risk Stratification.}},
author = {Yixiang Lian and Haijun Luo and Jing Zhou and Can Gong and Shali Jiang},
journal = {Cancer management and research},
year = {2026},
month = oct,
doi = {10.2147/cmar.s653756},
url = {https://europepmc.org/article/MED/42960123},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Heterogeneity of GYPC Methylation and p16/Ki67 Immunostaining in Cervical Intraepithelial Neoplasia: Implications for Risk Stratification.
AU - Yixiang Lian
AU - Haijun Luo
AU - Jing Zhou
AU - Can Gong
AU - Shali Jiang
PY - 2026
DA - 2026/10/25
JO - Cancer management and research
DO - 10.2147/cmar.s653756
UR - https://europepmc.org/article/MED/42960123
AB - Background GYPC methylation (GYPCm )is an early event in cancer transformation, whereas p16 and Ki67 are critical markers in cervical lesion pathology. This study aimed to explore the relationship between GYPCm status and the immunohistochemical markers p16, Ki67, and the combined immunostaining score (IS) in cervical lesions.Methods A retrospective analysis was conducted on 203 histologically confirmed cervical lesion specimens collected from October 2022 to July 2023. The specimens included 79 cases of cervical intraepithelial neoplasia (CIN) grade 1 (CIN1) (38.9%), 48 cases of CIN2 (23.6%), 66 cases of CIN3 (32.5%), and 10 cases of cervical squamous cell carcinoma (SCC; 4.9%). Immunohistochemical staining for p16 and Ki67, as well as GYPCm testing, was performed. The association between GYPCm and IS was assessed.Results GYPCm ΔCp decreased with increasing severity of cervical lesions (Cuzick trend test, P < 0.001). p16, Ki67, and IS showed an increasing trend with the severity of cervical lesions (all P trend < 0.001). Moreover, GYPCm increased with p16, Ki67, and IS (all P trend < 0.001). An IS of 5-6 and high GYPCm were observed in all SCC cases. Heterogeneity of GYPCm and IS was present in CIN: in CIN1, 15 cases had an IS of 3-4 with a moderate or high GYPCm . In CIN2, seven cases had an IS of 3-4 with low GYPCm .Conclusion Significant heterogeneity in IS and GYPCm exists in CIN. These findings suggest that GYPCm combined with p16/Ki67 immunostaining may be useful for risk stratification of cervical lesions. However, because this was a retrospective cross-sectional study without longitudinal follow-up, the value of these markers in predicting short-term cancer progression requires prospective validation before they can be used to guide personalized management.
SN - 1179-1322
ER -