中国癌症杂志 ›› 2020, Vol. 30 ›› Issue (8): 570-576.doi: 10.19401/j.cnki.1007-3639.2020.08.002

• 论著 • 上一篇    下一篇

宫颈鳞状上皮FoxM1及Cdc25B细胞核内蛋白水平与高危型HPV感染的相关性研究

梁 琳 1 ,万晓春 1 ,危 平 1 ,常 彬 1 ,向礼兵 2 ,朱琳琳 1 ,平 波 1   

  1. 1. 复旦大学附属肿瘤医院病理科,复旦大学上海医学院肿瘤学系,上海 200032 ;
    2. 复旦大学附属肿瘤医院妇瘤科,复旦大学上海医学院肿瘤学系,上海 200032
  • 出版日期:2020-08-30 发布日期:2020-09-03
  • 通信作者: 平 波 E-mail: bping2007@163.com
  • 基金资助:
    国家自然科学基金青年科学基金项目(81101956/H1621);上海市科学技术委员会科研计划项目(19MC1911000);上海市临床重点专科建设项目—病理科(shslczdzk01301)。

Nuclear FoxM1 and Cdc25B protein expressions correlate with high-risk HPV infection in cervical squamous epithelium

LIANG Lin 1 , WAN Xiaochun 1 , WEI Ping 1 , CHANG Bin 1 , XIANG Libing 2 , ZHU Linlin 1 , PING Bo 1   

  1. 1. Department of Pathology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 2. Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • Online:2020-08-30 Published:2020-09-03
  • Contact: PING Bo E-mail: bping2007@163.com

摘要: 背景与目的:宫颈癌是妇科最常见的恶性肿瘤,人乳头状瘤病毒(human papilloma virus,HPV)与宫颈癌/癌前病变的发生关系密切。宫颈组织活检RNA标本及宫颈癌细胞系中发现HPV 16 E7基因与FoxM1基因表达具有相关性。为发掘辅助诊断宫颈鳞癌及其癌前病变的免疫组织化学(immunohistochemistry,IHC)标志物,分析宫颈组织中高危型HPV感染(high-risk HPV,hrHPV)和转录因子FoxM1及其下游蛋白Cdc25B的细胞核内水平之间的相关性。方法:宫颈活检、锥切及子宫切除组织学标本来自复旦大学附属肿瘤医院病理科资料库(2007—2009年),用于细胞核FoxM1和Cdc25B蛋白IHC检测,并与23种基因型HPV DNA检测以及P16INK4a(P16)和Ki-67之IHC结果比较。结果:包括22例正常、28例CIN1、50例CIN2/3和40例鳞癌在内共计140例入组。CIN2+中hrHPV感染率100%(90/90),FoxM1、Cdc25B、P16和Ki-67阳性率分别为100.00%(90/90)、94.44%(85/90)、85.56%(77/90)和97.78%(88/90),且上述标志物阳性率均随宫颈病变严重程度加剧而上升(Jonckheere-Terpstra检验,P均<0.000 1)。FoxM1和Cdc25B表达与hrHPV感染、P16和Ki-67阳性率相关(Spearman相关检验,P均<0.000 1)。FoxM1和Cdc25B诊断CIN2+效果佳,曲线下面积(area under curve,AUC)值分别为0.850和0.822。结论:人宫颈鳞状上皮中细胞核FoxM1和Cdc25B蛋白水平与hrHPV感染相关,有望成为诊断与鉴别诊断CIN2+的潜在辅助指标。

关键词: 宫颈, 人乳头状瘤病毒, FoxM1, Cdc25B

Abstract: Background and purpose: Cervical cancer is the most common gynecological malignancy, and human papillomavirus (HPV) is closely related to cervical cancer/precancerous lesions. Correlation between expressions of HPV16 E7 and FoxM1 was found in cervical tissue biopsy RNA samples and cervical cancer cell lines. This study aimed to discover the potential immunohistochemical markers for cervical squamous cell carcinoma (SCC) and its precursor. We conducted correlation analysis for high-risk HPV (hrHPV) infection versus nuclear protein expressions of transcriptional factor FoxM1 and its downstream target Cdc25B using uterine cervical tissues. Methods: Histological samples obtained from cervical biopsy, conization or hysterectomy were collected from pathology archives of Fudan University Shanghai Cancer Center from 2007 to 2009. Nuclear expressions of FoxM1 and Cdc25B were evaluated by immunohistochemistry and compared with P16 and Ki-67 immunostaining, as well as HPV DNA tests for 23 genotypes. Results: A total of 140 cases were recruited, including normal (n=22), cervical intraepithelial neoplasia (CIN)1 (n=28), CIN2/3 (n=50) and SCC (n=40) specimens. The positive rates of hrHPV, FoxM1, Cdc25B, P16 and Ki-67 in CIN2+ were 100.00% (90/90), 100.00% (90/90), 94.44% (85/90), 85.56% (77/90) and 97.78% (88/90) respectively, and all rates increased with the severity of the disease (Jonckheere-Terpstra test, P<0.0001). FoxM1 and Cdc25B expressions correlated with hrHPV infection, P16 and Ki-67 (Spearman’s correlation test, P<0.0001). The area under the curve (AUC) values of FoxM1 and Cdc25B for diagnosing CIN2+ were 0.850 and 0.822, respectively. Conclusion: The correlation between hrHPV infection and FoxM1 or Cdc25B protein expression in cervical squamous epithelium was confirmed. Nuclear FoxM1 and Cdc25B proteins may be potential biomarkers for CIN2+.

Key words: Uterine cervix, Human papillomavirus, FoxM1, Cdc25B