Department of Oral Pathology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland.
Int J Gynecol Pathol. 2010 Mar;29(2):135-45. doi: 10.1097/PGP.0b013e3181bccaec.
To evaluate the role of the expression of the transcription factor p300 as an independent predictor of high-risk human papillomavirus (HR-HPV) infections and outcome of the cervical disease.Cervical biopsy samples taken at enrolment from 225 women of the Latin American Screening study cohort were analyzed for p300 using immunohistochemistry to assess its value as predictor of (a) cervical intraepithelial neoplasia (CIN) grade, and (b) HR-HPV at baseline, as well as (c) outcomes of HR-HPV infections, and (d) development of incident CIN as surrogate endpoints of progressive disease.There was a significant linear trend in increasing upregulation (=pattern shift) of p300 (P=0.0001) in parallel with increasing grade of CIN. When dichotomized (normal/moderately increase vs. strong-intense), upregulated p300 expression predicted CIN3+ with odds ratio=4.16 (95% confidence interval: 1.95-8.86) (P=0.0001) and CIN2+ with odds ratio=3.48 (95% confidence interval: 1.86-6.48) (P=0.0001). p300 was upregulated more often in HR-HPV+ lesions than in those remaining negative. Semiquantitative viral loads were also directly related to upregulation of p300 (P=0.036), but p300 was not a significant predictor of disease progression to either CIN1+ or CIN2+.p300 expression was upregulated in CIN lesions and related to detection and viral load of HR-HPV but not to their outcome or to incident CIN.
评估转录因子 p300 的表达作为高危型人乳头瘤病毒(HR-HPV)感染和宫颈疾病结局的独立预测因子的作用。使用免疫组织化学分析拉丁美洲筛查研究队列中 225 名女性入组时的宫颈活检样本中 p300 的表达,以评估其作为(a)宫颈上皮内瘤变(CIN)分级和(b)基线时 HR-HPV 的预测因子的价值,以及(c)HR-HPV 感染的结局,以及(d)以新发 CIN 为替代终点的进展性疾病的发展。随着 CIN 分级的增加,p300 的上调(=模式改变)呈显著线性趋势(P=0.0001)。当二分类(正常/中度增加与强-强烈)时,上调的 p300 表达预测 CIN3+的优势比=4.16(95%置信区间:1.95-8.86)(P=0.0001)和 CIN2+的优势比=3.48(95%置信区间:1.86-6.48)(P=0.0001)。p300 在 HR-HPV+病变中上调的频率高于那些仍然为阴性的病变。半定量病毒载量也与 p300 的上调直接相关(P=0.036),但 p300 不是疾病进展为 CIN1+或 CIN2+的显著预测因子。p300 在 CIN 病变中上调,并与 HR-HPV 的检测和病毒载量相关,但与它们的结局或新发 CIN 无关。