Karkas Réka, Abdullah Khaldoon Sadiq Ahmed, Kaizer László, Ürmös Ádám, Raya May, Tiszlavicz Lilla, Pankotai Tibor, Nagy István, Mátés Lajos, Sükösd Farkas
Laboratory of Cancer Genome Research, Institute of Genetics, HUN-REN Biological Research Centre, Szeged, Hungary.
Doctoral School of Multidisciplinary Medical Sciences, University of Szeged, Albert Szent-Györgyi Medical School, Szeged, Hungary.
Int J Gynecol Pathol. 2025 Jan 1;44(1):22-30. doi: 10.1097/PGP.0000000000001035. Epub 2024 Jun 26.
Cervical intraepithelial neoplasia (CIN) represents a spectrum of preinvasive squamous lesions within the cervical epithelium, whose identification is a diagnostic challenge due to subtle histomorphological differences among its categories. This study explores ORF1p, a nucleic acid-binding protein derived from long interspersed nuclear element-1 (LINE-1), as a potential biomarker for enhancing CIN diagnosis. A comprehensive analysis of 143 cervical specimens, encompassing CIN I (n=20), CIN II (n=46), CIN III (n=14), invasive cancer (n=32), and nondysplastic cases (normal cervical epithelia (n=24) and atrophy (n=7) were conducted. ORF1p, Ki67, and p16 expressions were evaluated using immunohistochemistry. ORF1p immunopositivity was detected in the vast majority [110/112 (98.2%)] of dysplastic and neoplastic (CIN and invasive cancer) specimens, whereas 19/24 (79.2%) of normal cervical specimens lacked ORF1p expression. The observed pattern of ORF1p expression showed a progressively increasing extent and intensity with advancing CIN grades. CIN I exhibited mild ORF1p expression in the lower one or two-thirds of the cervical epithelium [14/16 (87.5%)], whereas CIN II demonstrated moderate to strong ORF1p expression spanning the lower two-thirds [29/46 (63.0%)]. Pronounced transepithelial ORF1p immunopositivity characterized CIN III cases [13/14 (92.8%)] and cervical cancer [30/32 (93.8%)]. These findings propose ORF1p as a valuable indicator even for detecting CIN I, effectively discerning them from normal cervical tissue (p < 0.0001). Our findings underscore the potential of ORF1p as an early diagnostic marker for cervical neoplasia.
宫颈上皮内瘤变（CIN）代表宫颈上皮内一系列鳞状上皮的浸润前病变，由于其不同类别之间细微的组织形态学差异，对其进行识别是一项诊断挑战。本研究探索了开放阅读框1蛋白（ORF1p），一种源自长散在核元件1（LINE-1）的核酸结合蛋白，作为增强CIN诊断的潜在生物标志物。对143例宫颈标本进行了全面分析，包括CIN I（n = 20）、CIN II（n = 46）、CIN III（n = 14）、浸润性癌（n = 32）以及非发育异常病例（正常宫颈上皮（n = 24）和萎缩（n = 7））。采用免疫组织化学方法评估ORF1p、Ki67和p16的表达。在绝大多数发育异常和肿瘤性（CIN和浸润性癌）标本[110/112（98.2%）]中检测到ORF1p免疫阳性，而19/24（79.2%）的正常宫颈标本缺乏ORF1p表达。观察到的ORF1p表达模式显示，随着CIN分级的进展，其程度和强度逐渐增加。CIN I在宫颈上皮下三分之一或下三分之二处表现为轻度ORF1p表达[14/16（87.5%）]，而CIN II表现为中度至强的ORF1p表达，跨越下三分之二[29/46（63.0%）]。CIN III病例[13/14（92.8%）]和宫颈癌[30/32（93.8%）]的特征是显著的跨上皮ORF1p免疫阳性。这些发现表明，ORF1p即使对于检测CIN I也是一个有价值的指标，能有效地将它们与正常宫颈组织区分开来（p < 0.0001）。我们的研究结果强调了ORF1p作为宫颈肿瘤早期诊断标志物的潜力。
