Thuijs Nikki B, Schonck Willemijn A M, Klaver Linde L J, Fons Guus, van Beurden Marc, Steenbergen Renske D M, Bleeker Maaike C G
Department of Pathology, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Department of Gynecology, Universiteit van Amsterdam, Amsterdam UMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Cancers (Basel). 2021 Nov 11;13(22):5646. doi: 10.3390/cancers13225646.
In patients with high-grade squamous intraepithelial lesion (HSIL) of the vulva, the presence of multiple lesions, called multifocal HSIL, is common. The aim of this exploratory study was to investigate biomarker expression profiles in multifocal HSIL. In total, 27 lesions from 12 patients with high-risk human papillomavirus (HPV)-positive multifocal HSIL were tested for HPV genotype, expression of p16 and Ki-67, and DNA methylation of six genes. HPV16 was found most commonly in 21 (77.8%) HSILs. In two (16.4%) patients, HPV genotype differed between the lesions. All lesions demonstrated diffuse p16 staining, of which three (11.1%) were combined with patchy staining. One patient (8.3%) demonstrated markedly different DNA methylation levels between lesions. Generally, heterogeneity in methylation profiles was observed between different patients, even when other biomarkers showed similar expression. In conclusion, this study is the first to demonstrate heterogeneity of individual lesions in patients with multifocal HSIL. The studied biomarkers have the potential to refine prognostic and predictive diagnostics. Future prospective, longitudinal studies are needed to further explore the potential of a biomarker profile for management of patients with multifocal HSIL.
在外阴高级别鳞状上皮内病变（HSIL）患者中，存在多个病变即多灶性HSIL的情况很常见。这项探索性研究的目的是调查多灶性HSIL中的生物标志物表达谱。总共对12例高危人乳头瘤病毒（HPV）阳性多灶性HSIL患者的27个病变进行了HPV基因型、p16和Ki-67表达以及6个基因的DNA甲基化检测。HPV16最常见于21个（77.8%）HSIL中。在2例（16.4%）患者中，不同病变的HPV基因型不同。所有病变均显示p16弥漫性染色，其中3个（11.1%）伴有斑片状染色。1例患者（8.3%）的不同病变之间DNA甲基化水平存在明显差异。总体而言，即使其他生物标志物表达相似，不同患者之间甲基化谱也存在异质性。总之，本研究首次证明了多灶性HSIL患者个体病变的异质性。所研究的生物标志物有潜力优化预后和预测诊断。未来需要进行前瞻性纵向研究，以进一步探索生物标志物谱在多灶性HSIL患者管理中的潜力。
