Quade B J, Park J J, Crum C P, Sun D, Dutta A
Division of Women's Pathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mod Pathol. 1998 Dec;11(12):1238-46.
Identification of human papillomavirus (HPV)-related early cervical neoplasia and its distinction from benign epithelial alterations is based on either subjectively applied morphologic criteria or on identification of associated papillomaviruses. The direct and indirect consequences of HPV infection, however, potentially include upregulation of some host genes. We investigated one candidate, cyclin E, as a possible marker for HPV-related early squamous lesions. Serial paraffin sections from 92 archival cervical biopsy specimens were analyzed, including 19 non-neoplastic biopsy specimens, 30 low-grade and 31 high-grade squamous intraepithelial lesions (SILs), and 12 invasive carcinomas. Four parameters (histologic diagnosis, cyclin E staining, HPV status and, in selected cases, Ki-67 staining) were scored, and their relationship(s) were evaluated by the chi2 independence test. Twenty-one, 73, 79, and 75% of nonlesional epithelia, low-grade SILs, high-grade SILs, and invasive squamous cell carcinomas, respectively, were HPV positive (P < .001 for HPV status vs. diagnosis). Cyclin E staining was nuclear in distribution, and the frequency of positive staining, ie., moderate or strong intensity, was significantly higher (P < .001 for cyclin E staining vs. diagnosis) in all of the lesional epithelia (92.3, 51.6, and 50% of low-grade and high-grade SILs and carcinomas, respectively) compared with nonlesional epithelium (5.9%). Cyclin E positivity and/or HPV positivity was seen in 100% of the low-grade SILs. Epithelial Ki-67 and cyclin E staining were strikingly different in frequency and distribution. Cyclin E was undetectable in basal cells of normal mucosa (which were positive for Ki-67) and limited to suprabasal epithelium in noninvasive lesions. Cyclin E expression correlates strongly with morphologic features of HPV-related preinvasive and invasive cervical disease. This correlation is most pronounced in low-grade SILs. The possibility that in vivo cyclin E staining is a generic marker for HPV infection in low-grade SILs merits additional study.
人乳头瘤病毒（HPV）相关的早期宫颈肿瘤的识别及其与良性上皮改变的区分，是基于主观应用的形态学标准或相关乳头瘤病毒的识别。然而，HPV感染的直接和间接后果可能包括一些宿主基因的上调。我们研究了细胞周期蛋白E这一候选指标，将其作为HPV相关早期鳞状病变的可能标志物。对92份存档宫颈活检标本的连续石蜡切片进行了分析，包括19份非肿瘤性活检标本、30份低级别和31份高级别鳞状上皮内病变（SIL）以及12份浸润性癌。对四个参数（组织学诊断、细胞周期蛋白E染色、HPV状态以及在选定病例中的Ki-67染色）进行评分，并通过卡方独立性检验评估它们之间的关系。分别有21%、73%、79%和75%的非病变上皮、低级别SIL、高级别SIL和浸润性鳞状细胞癌HPV呈阳性（HPV状态与诊断相比，P <.001）。细胞周期蛋白E染色呈核分布，在所有病变上皮中，阳性染色的频率，即中度或强强度，显著更高（细胞周期蛋白E染色与诊断相比，P <.001），低级别和高级别SIL以及癌分别为92.3%、51.6%和50%，而非病变上皮为5.9%。100%的低级别SIL中可见细胞周期蛋白E阳性和/或HPV阳性。上皮Ki-67和细胞周期蛋白E染色在频率和分布上明显不同。正常黏膜的基底细胞中未检测到细胞周期蛋白E（其Ki-67呈阳性），在非浸润性病变中仅限于基底上层上皮。细胞周期蛋白E表达与HPV相关的宫颈前浸润性和浸润性疾病的形态学特征密切相关。这种相关性在低级别SIL中最为明显。体内细胞周期蛋白E染色作为低级别SIL中HPV感染的通用标志物的可能性值得进一步研究。
