Hu Wan-Hsiang, Miyai Katsumi, Sporn Judith C, Luo Linda, Wang Jean Y J, Cosman Bard, Ramamoorthy Sonia
Department of Surgery, University of California San Diego Health System, San Diego, California, USA Rebecca and John Moores Cancer Center, University of California San Diego Health System, San Diego, California, USA Department of Colorectal Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Department of Pathology, School of Medicine, University of California, San Diego, California, USA.
J Clin Pathol. 2016 Jul;69(7):627-31. doi: 10.1136/jclinpath-2015-203367. Epub 2015 Dec 10.
The macroH2A histone variants are epigenetic marks for inactivated chromatin. In this study, we examined the expression of macroH2A2 in anal neoplasm from anal intraepithelial neoplasia (AIN) to anal squamous cell carcinoma (SCC).
AIN and anal SCC samples were analysed for macroH2A2 expression, HIV and human papilloma virus (HPV). The association of macroH2A2 expression with clinical grade, disease recurrence, overall survival and viral involvement was determined.
macroH2A2 was expressed in normal squamous tissue and lower grade AIN (I and II). Expression was lost in 38% of high-grade AIN (III) and 71% of anal SCC (p=0.002). Patients with AIN with macroH2A2-negative lesions showed earlier recurrence than those with macroH2A2-positive neoplasm (p=0.017). With anal SCC, macroH2A2 loss was more prevalent in the HPV-negative tumours.
Loss of histone variant macroH2A2 expression is associated with the progression of anal neoplasm and can be used as a prognostic biomarker for high-grade AIN and SCC.
巨H2A组蛋白变体是染色质失活的表观遗传标记。在本研究中,我们检测了从肛管上皮内瘤变(AIN)到肛管鳞状细胞癌(SCC)的肛管肿瘤中巨H2A2的表达情况。
对AIN和肛管SCC样本进行巨H2A2表达、HIV和人乳头瘤病毒(HPV)分析。确定巨H2A2表达与临床分级、疾病复发、总生存期和病毒感染的相关性。
巨H2A2在正常鳞状组织和低级别AIN(I级和II级)中表达。在38%的高级别AIN(III级)和71%的肛管SCC中表达缺失(p=0.002)。巨H2A2阴性病变的AIN患者比巨H2A2阳性肿瘤患者复发更早(p=0.017)。在肛管SCC中,巨H2A2缺失在HPV阴性肿瘤中更为普遍。
组蛋白变体巨H2A2表达缺失与肛管肿瘤进展相关,可作为高级别AIN和SCC的预后生物标志物。