Svanadze Tamar, Turashvili Teona, Kepuladze Shota, Burkadze George
Obstetrics and Gynecology, Tbilisi State Medical University, Tbilisi, GEO.
Pathology and Oncology, Tbilisi State Medical University, Tbilisi, GEO.
Cureus. 2025 Apr 3;17(4):e81661. doi: 10.7759/cureus.81661. eCollection 2025 Apr.
Cervical intraepithelial neoplasia (CIN) is a well-established precursor of cervical cancer, while immature polypoid squamous metaplasia (IPM) has been hypothesized as a possible early lesion in cervical carcinogenesis. However, the mechanisms underlying IPM progression to CIN remain unclear. Therefore, identifying reliable biomarkers to predict progression is crucial. This study evaluates the immunohistochemical expression of P16, CD44, estrogen receptor (ER), and progesterone receptor (PR) in CIN and IPM, focusing on their prognostic significance in IPM-to-CIN progression. A total of 227 cervical tissue samples were analyzed, including CIN1 (N=30), CIN2 (N=30), CIN3 (N=32), IPM (N=60), mature squamous metaplasia (N=45), and reactive ectocervix - control (N=30). P16, CD44, ER, and PR expression were assessed immunohistochemically. Additionally, clinical HPV (human papillomavirus) status was determined via PCR, and marker expression was correlated with lesion grade using a standardized study algorithm. A subgroup of 40 IPM cases that progressed to CIN was analyzed to identify possible markers predictive of progression. Our results demonstrate that higher P16 and CD44 expression levels are significantly associated with higher-grade CIN lesions (p < 0.001). P16 and CD44 expression also strongly predicted IPM progression: P16 showed a 100% positive predictive value (PPV) for progression to CIN2 or CIN3, meaning all IPM cases with moderate or strong P16 expression advanced to high-grade CIN. CD44 had a 90% PPV for CIN progression, suggesting a strong correlation with aggressive epithelial transformation. Although ER and PR expressions were statistically significant (p < 0.05), they were not predictive markers of CIN progression. These findings highlight P16 and CD44 as possible biomarkers for identifying high-risk IPM lesions and assessing the likelihood of progression to CIN2/3.
宫颈上皮内瘤变（CIN）是公认的宫颈癌前病变，而未成熟息肉样鳞状化生（IPM）被认为是宫颈癌发生过程中一种可能的早期病变。然而，IPM进展为CIN的潜在机制仍不清楚。因此，识别可靠的生物标志物以预测进展至关重要。本研究评估了P16、CD44、雌激素受体（ER）和孕激素受体（PR）在CIN和IPM中的免疫组化表达，重点关注它们在IPM进展为CIN过程中的预后意义。共分析了227例宫颈组织样本，包括CIN1（n = 30）、CIN2（n = 30）、CIN3（n = 32）、IPM（n = 60）、成熟鳞状化生（n = 45）和反应性宫颈外口——对照（n = 30）。采用免疫组化方法评估P16、CD44、ER和PR的表达。此外，通过PCR确定临床人乳头瘤病毒（HPV）状态，并使用标准化研究算法将标志物表达与病变分级相关联。对40例进展为CIN的IPM病例亚组进行分析，以确定可能预测进展的标志物。我们的结果表明，较高的P16和CD44表达水平与高级别CIN病变显著相关（p < 0.001）。P16和CD44表达也强烈预测IPM进展：P16对进展为CIN2或CIN3的阳性预测值（PPV）为100%，这意味着所有P16表达为中度或强阳性的IPM病例都进展为高级别CIN。CD44对CIN进展的PPV为90%，表明与侵袭性上皮转化密切相关。虽然ER和PR表达具有统计学意义（p < 0.05），但它们不是CIN进展的预测标志物。这些发现突出了P16和CD44作为识别高危IPM病变和评估进展为CIN2/3可能性的可能生物标志物。
