Department of Pathology, Cathay General Hospital, Taipei 106, Taiwan.
Hum Pathol. 2010 Mar;41(3):326-35. doi: 10.1016/j.humpath.2009.05.015. Epub 2009 Dec 1.
Most human papillomavirus-associated squamous intraepithelial lesions of the uterine cervix are flat; some have papillary architecture that shows a spectrum of differentiation from low-grade squamous intraepithelial lesions to high-grade squamous intraepithelial lesions. For this subset of lesions, there are few data relating human papillomavirus type to cytology and cell cycle activity. Here, we collected 24 cases of papillary squamous intraepithelial lesions with either low-risk (15 cases) or high-risk (9 cases) human papillomavirus infection. We described their morphology and performed immunohistochemical staining with cell cycle-related markers Ki-67, p53, pRb, and P16INK4a. The Ki-67 labeling index was significantly lower in the low-risk group than in the high-risk group (P < .001). A cut point of less than 50% labeling index detected all but one low-risk group case. Degradation of p53 and pRb was less evident in the low-risk group than in the high-risk group (p53, P < .001; pRb, P = .006). P16INK4a produced an unexpectedly high positive rate of staining in the low-risk group (60%). However, a specific top-heavy distribution pattern was noted, with evident nuclear but faint cytoplasmic staining, whereas the high-risk group showed strong full-thickness nuclear and cytoplasmic staining. The detection of these lesions by smear examination was not reliable, given the wide expression pattern. Papillary structure was evident in none. We conclude that cell cycle-related markers are helpful in distinguishing low- and high-risk lesions. The strong p16INK4a staining in the low-risk group may imply that more cell cycle-controlling pressure is elicited in papillary lesions than in flat lesions. The distribution pattern of p16INK4a staining is important when making a diagnosis; cytology is not effective. Human papillomavirus type, histology, and cell cycle markers could clearly separate these lesions into either a low-risk or a high-risk group, properly designated low-grade squamous intraepithelial lesions or high-grade squamous intraepithelial lesions in current management algorithms. Thus, the previously used terms papillary immature metaplasia and immature condyloma, although descriptive for low-risk group lesions, are confusing and should be discarded.
大多数人乳头瘤病毒相关的子宫颈鳞状上皮内病变为扁平型；有些具有乳头状结构，显示出从低级别鳞状上皮内病变到高级别鳞状上皮内病变的分化谱。对于这部分病变，有关人乳头瘤病毒类型与细胞学和细胞周期活性的关系的数据很少。在这里，我们收集了 24 例具有低危型（15 例）或高危型（9 例）人乳头瘤病毒感染的乳头状鳞状上皮内病变。我们描述了它们的形态，并进行了与细胞周期相关的标志物 Ki-67、p53、pRb 和 P16INK4a 的免疫组织化学染色。低危组的 Ki-67 标记指数明显低于高危组（P <.001）。Ki-67 标记指数小于 50%的截断值可检测出除一个低危组病例之外的所有病例。低危组中 p53 和 pRb 的降解比高危组更为明显（p53，P <.001；pRb，P =.006）。P16INK4a 在低危组中产生了出乎意料的高阳性率（60%）。然而，观察到一种特定的头重脚轻的分布模式，具有明显的核染色但细胞质染色较弱，而高危组则显示出强烈的全层核和细胞质染色。鉴于广泛的表达模式，通过涂片检查检测这些病变不可靠。乳头状结构在任何情况下都不明显。我们得出结论，细胞周期相关标志物有助于区分低危和高危病变。高危组中 p16INK4a 的强染色可能意味着在乳头状病变中比在扁平病变中引起更多的细胞周期控制压力。在做出诊断时，p16INK4a 染色的分布模式很重要；细胞学效果不佳。人乳头瘤病毒类型、组织学和细胞周期标志物可以清楚地将这些病变分为低危或高危组，在当前的管理算法中正确指定为低级别鳞状上皮内病变或高级别鳞状上皮内病变。因此，以前使用的术语乳头状不成熟化生和不成熟尖锐湿疣虽然对低危组病变具有描述性，但容易引起混淆，应予以摒弃。
