Chu Hyun Hee, Bae Jun Sang, Kim Kyoung Min, Park Ho Sung, Cho Dong Hyu, Jang Kyu Yun, Moon Woo Sung, Kang Myoung Jae, Lee Dong Geun, Chung Myoung Ja
Department of Pathology, Chonbuk National University Medical School, Jeonju, Korea.
Korean J Pathol. 2012 Oct;46(5):463-9. doi: 10.4132/KoreanJPathol.2012.46.5.463. Epub 2012 Oct 25.
High-risk human papillomavirus (HR-HPV) infection and abnormal p53 expression are closely involved in carcinogenesis of squamous cell carcinoma (SqCC) of uterine cervix. Recent studies have suggested that virus-induced endoplasmic reticulum (ER) stress modulates various cell survival and cell death signaling pathways. The C/EBP homologous protein (CHOP) is associated with ER stress-mediated apoptosis and is also involved in carcinogenesis of several human cancers. We hypothesized that CHOP is involved in the carcinogenesis of uterine cervical cancer in association with HR-HPV and/or p53.
Immunohistochemistry was used to analyze CHOP and p53 protein expression of tissue sections from 191 patients with invasive cancer or preinvasive lesions of the uterine cervix (61 cases of SqCC, 66 cases of cervical intraepithelial neoplasia [CIN] III, and 64 cases of CIN I).
CHOP was expressed in 59.4% of CIN I, 48.5% of CIN III, and 70.5% of SqCC cases. It was also significantly more frequent in invasive SqCC than in preinvasive lesions (p=0.042). Moreover, CHOP expression significantly correlated with HR-HPV infection and p53 expression (p=0.009 and p=0.038, respectively).
Our results suggest that CHOP is involved in the carcinogenesis of the uterine cervix SqCC via association with HR-HPV and p53.
高危型人乳头瘤病毒(HR-HPV)感染和p53表达异常与子宫颈鳞状细胞癌(SqCC)的致癌作用密切相关。最近的研究表明,病毒诱导的内质网(ER)应激可调节各种细胞存活和细胞死亡信号通路。C/EBP同源蛋白(CHOP)与ER应激介导的细胞凋亡有关,也参与了几种人类癌症的致癌过程。我们假设CHOP与HR-HPV和/或p53相关,参与子宫颈癌的致癌过程。
采用免疫组织化学方法分析191例子宫颈浸润癌或癌前病变患者(61例SqCC、66例宫颈上皮内瘤变[CIN]III和64例CIN I)组织切片中CHOP和p53蛋白的表达。
CHOP在59.4%的CIN I、48.5%的CIN III和70.5%的SqCC病例中表达。在浸润性SqCC中,CHOP的表达也显著高于癌前病变(p=0.042)。此外,CHOP表达与HR-HPV感染和p53表达显著相关(分别为p=0.009和p=0.038)。
我们的结果表明,CHOP通过与HR-HPV和p53相关,参与子宫颈SqCC的致癌过程。