Tissue transglutaminase 2 as a biomarker of cervical intraepithelial neoplasia (CIN) and its relationship to p16INK4A and nuclear factor κB expression
Tissue transglutaminase 2 as a biomarker of cervical intraepithelial neoplasia (CIN) and its relationship to p16INK4A and nuclear factor κB expression
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DOI：
10.1007/s00428-009-0860-5
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发表时间：
2010-01-01
期刊：
影响因子：
3.5
通讯作者：
Suri, Vanita
中科院分区：
文献类型：
--
作者：
Gupta, Ruchi;Srinivasan, Radhika;Suri, Vanita
组织转谷氨酰胺酶2 （TG2）是最近发现的具有多种生理功能的分子。这是首次报道TG2在宫颈上皮内瘤变（CIN）和浸润性鳞状细胞癌（SCC）中的表达。为了进行比较，我们评估了已知的HPV感染替代生物标志物p16的表达。核因子κ B （nf - κ B）是炎症和肿瘤发生的关键分子，其表达也被测定，以探索其与TG2表达的可能联系。采用免疫组化方法分析20例宫颈组织学正常、CIN1、CIN2、CIN3及侵袭性SCC患者TG2、p16及NF-kappa B的表达。组间差异采用Friedman ANOVA分析。在上皮细胞中观察到细胞质和细胞核中TG2的表达。与正常对照相比，CIN1细胞胞质TG2表达明显增加（p = 0.006）。在CIN2/3中，核TG2额外表达（p分别= 0.009和0.031）。与正常对照相比，CIN3/SCC组细胞外基质TG2明显上调（p = 0.054; p = 0.003）。TG2与NF-kappa B的p16表达均无相关性。将TG2免疫反应性与p16结合使用，使CIN1的免疫标记率从35%提高到100%，CIN2从45%提高到60%，CIN3从60%提高到85%。TG2可作为所有级别宫颈发育不良，特别是低级别宫颈发育不良的额外生物标志物。
Tissue transglutaminase 2 (TG2) is a recently identified molecule with multifunctional physiological roles. This is the first report of the expression of TG2 in cervical intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma (SCC). For comparison, the expression of p16, a known surrogate biomarker of HPV infection, was evaluated. The expression of nuclear factor kappa B (NF-kappa B), a molecule crucial to inflammation and neoplasia, was also determined to explore its possible linkage with TG2 expression. Twenty cases each with normal cervical histology, CIN1, CIN2, CIN3, and invasive SCC were analyzed for TG2, p16, and NF-kappa B expression by immunohistochemistry. Intergroup differences were analyzed by Friedman ANOVA. Cytoplasmic as well as nuclear TG2 expression was observed in the epithelial cells. As compared to normal controls, CIN1 showed markedly increased cytoplasmic TG2 expression (p = 0.006). In CIN2/3, additional nuclear TG2 expression was seen (p = 0.009 and 0.031, respectively). Marked extracellular stromal upregulation of TG2 was noted in CIN3/SCC versus normal controls (p = 0.054; p = 0.003). There was no relationship of TG2 with either p16 of NF-kappa B expression. Combining TG2 immunoreactivity with p16 increased the immunolabeling of dysplasia from 35% to 100% in CIN1, 45% to 60% in CIN2, and 60% to 85% in CIN3. TG2 serves as an additional biomarker for all grades of cervical dysplasia, especially for low-grade dysplasia.