Wang Yanling, Lin Alexander Y, Wang Daisy Dandan, Lin Peter Ping, Zhou Xuexin, Yang Yongbin, Zhu Yaping
Department of Gynecology and Obstetrics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cytelligen, San Diego, CA, USA.
BMC Cancer. 2025 May 26;25(1):945. doi: 10.1186/s12885-025-14346-y.
To distinguish and co-detect aneuploid CD31 tumor cells (TCs) and CD31 tumor endothelial cells (TECs) may have significant diagnostic values for cervical cancer screening. However, there are very few relevant studies. In the present study, a novel "immunofluorescence staining integrated with fluorescence in situ hybridization (iFISH)" tumor tissue biopsy platform was applied to comprehensively investigate the clinical utilities of aneuploid TCs and TECs in all-stage cervical lesion smear specimens.
A total of 196 patients were enrolled in this study. Immunofluorescence staining of p16 and Ki67 combined with FISH was applied to quantitatively co-detect and characterize subcategorized aneuploid CD31 TCs and CD31 TECs in cervical cytological specimens. The Kruskal‒Wallis H test was used to compare the distributions of aneuploid TCs and TECs among all stages of cervical lesions and among the different high-risk HPV types (HPV16/18 and non-HPV16/18). The diagnostic value of detecting aneuploid TCs and TECs for high-grade squamous intraepithelial lesions (HSIL) was investigated via receiver operating characteristic curve analysis.
The number of total aneuploid CD31 TCs and their p16 and/or Ki67 (p16/Ki67) subtypes increased markedly with the severity of cervical lesions, although a similar trend was not observed for aneuploid CD31 TECs. The increase in aneuploid TCs resulted from HPV16/18 infection was mainly concentrated in low-grade squamous intraepithelial lesion(LSIL), whereas the increase caused by non-HPV16/18 infection was mainly concentrated in HSIL. To identify HSIL, the area under the curve (AUC) of tetraploid TCs was the largest (0.739), followed by multiploid (≥ pentaploid) TCs (0.724) and triploid TCs (0.699). For the combined subtypes, the AUC of ≥ tetraploid TCs was 0.745, and their unique diagnostic value was clinically reflected by their high specificity.
The quantity of CD31 aneuploid TCs was associated with the severity of cervical lesions. In HPV16/18 positive patients, aneuploid CD31 TCs were significantly increased in the LSIL. Moreover, aneuploid CD31 TCs exhibited remarkable specificity for detecting HSIL. Further studies are required to expand the potential clinical utility of detecting CD31 aneuploid TCs.
区分并共同检测非整倍体CD31肿瘤细胞（TCs）和CD31肿瘤内皮细胞（TECs）对宫颈癌筛查可能具有重要的诊断价值。然而，相关研究非常少。在本研究中，一种新型的“免疫荧光染色与荧光原位杂交相结合（iFISH）”肿瘤组织活检平台被应用于全面研究非整倍体TCs和TECs在各期宫颈病变涂片标本中的临床应用价值。
本研究共纳入196例患者。采用p16和Ki67免疫荧光染色结合FISH技术，对宫颈细胞学标本中的非整倍体CD31 TCs和CD31 TECs进行定量共同检测和亚分类特征分析。采用Kruskal-Wallis H检验比较非整倍体TCs和TECs在宫颈病变各期以及不同高危人乳头瘤病毒类型（HPV16/18和非HPV16/18）中的分布情况。通过绘制受试者工作特征曲线分析检测非整倍体TCs和TECs对高级别鳞状上皮内病变（HSIL）的诊断价值。
随着宫颈病变严重程度的增加，非整倍体CD31 TCs的总数及其p16和/或Ki67（p16/Ki67）亚型显著增加，而非整倍体CD31 TECs未观察到类似趋势。HPV16/18感染导致的非整倍体TCs增加主要集中在低级别鳞状上皮内病变（LSIL），而非HPV16/18感染导致的增加主要集中在HSIL。为了识别HSIL，四倍体TCs的曲线下面积（AUC）最大（0.739），其次是多倍体（≥五倍体）TCs（0.724）和三倍体TCs（0.699）。对于联合亚型，≥四倍体TCs的AUC为0.745，其独特的诊断价值在临床上表现为高特异性。
CD31非整倍体TCs的数量与宫颈病变的严重程度相关。在HPV16/18阳性患者中，LSIL中非整倍体CD31 TCs显著增加。此外，非整倍体CD31 TCs在检测HSIL方面表现出显著的特异性。需要进一步研究以扩大检测CD31非整倍体TCs的潜在临床应用价值。
