De Marchi Triglia Renata, Metze Konradin, Zeferino Luiz Carlos, Lucci De Angelo Andrade Liliana A
Department of Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
Gynecol Oncol. 2009 Jan;112(1):114-8. doi: 10.1016/j.ygyno.2008.09.047. Epub 2008 Nov 12.
HPV-DNA integration is one factor for malignant transformation and can be identified using in situ hybridization (ISH), where a diffuse signal represents episomal HPV and punctate, integrated. The aim is to verify if a punctate pattern could be a marker of CIN1 that progresses.
74 CIN1 biopsies were studied. In the follow up, a second biopsy was performed and 65% showed CIN1 or no lesion (group without progression) and 35% CIN2/3 (with progression). ISH was carried out with HR-HPV GenPoint in the first biopsy looking for the positive distribution in epithelium regions (basal, intermediate, superficial) and reaction pattern (diffuse and punctate). The Mann-Whitney and Fisher tests were used to compare the groups (p<or=0.05).
The mean age of patients without progression was 26 and, with progression 31 (p=0.02). ISH was positive in 22 cases, 8 with CIN2/3 in the second biopsy. The punctate signal was observed in all epithelial layers, and the mean coefficient between the number of cells with punctate and diffuse signals was 3.5 times more common in the progression group (p=0.08). The average percentage of punctate nuclei patterns in the basal region in cases without progression was 0.5% and 11% in those with progression (p=0.05). However, in superficial layer this was not correlated with progression.
Progression was observed in 35% of CIN1 and associated with age; 30% of the cases were positive by ISH, but must be carefully interpreted. Punctate signals were related to progression only in basal cells, identifying CIN1 with potentially aggressive behavior.
人乳头瘤病毒（HPV）-DNA整合是恶性转化的一个因素，可通过原位杂交（ISH）进行识别，其中弥漫性信号代表游离型HPV，点状信号代表整合型。目的是验证点状模式是否可能是进展性CIN1的一个标志物。
对74例CIN1活检样本进行研究。在随访过程中，进行了第二次活检，65%显示为CIN1或无病变（无进展组），35%为CIN2/3（有进展组）。在第一次活检中使用HR-HPV GenPoint进行ISH，寻找上皮区域（基底、中层、表层）的阳性分布和反应模式（弥漫性和点状）。使用Mann-Whitney检验和Fisher检验对两组进行比较（p≤0.05）。
无进展患者的平均年龄为26岁，有进展患者为31岁（p=0.02）。ISH在22例中呈阳性，其中8例在第二次活检中为CIN2/3。在所有上皮层均观察到点状信号，点状信号与弥漫性信号细胞数量的平均系数在进展组中多3.5倍（p=0.08）。无进展病例基底区域点状核模式的平均百分比为0.5%，有进展病例为11%（p=0.05）。然而，在表层，这与进展无关。
35%的CIN1出现进展，且与年龄相关；30%的病例ISH呈阳性，但必须谨慎解读。点状信号仅在基底细胞中与进展相关，可识别具有潜在侵袭性行为的CIN1。
