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首页> 外文期刊>International journal of gynecological pathology: Official journal of the International Society of Gynecological Pathologists >Expression of phosphorylated histone H2AX (gamma-H2AX) in normal and neoplastic squamous epithelia of the uterine cervix: an immunohistochemical study with epidermal growth factor receptor.
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Expression of phosphorylated histone H2AX (gamma-H2AX) in normal and neoplastic squamous epithelia of the uterine cervix: an immunohistochemical study with epidermal growth factor receptor.

机译：磷酸化组蛋白H2AX（γ-H2AX）在正常和子宫颈鳞状上皮中的表达：一项利用表皮生长因子受体的免疫组织化学研究。

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摘要

The histone gamma-H2AX is a marker of activated DNA damage and is overexpressed in different cancers and their precursor lesions, indicating a role in oncogenic transformation. Epidermal growth factor receptor (EGFR) is overexpressed in many kinds of epithelial neoplasms. This study aimed to determine whether immunohistochemical expression of gamma-H2AX is involved in the progression of the morphological spectrum from normal squamous cervical epithelia (NE, n=33) to cervical intraepithelial neoplasia (CIN; CIN1, n=9; CIN2/3, n=33) and cervical invasive squamous cell carcinoma (ISCC, n=33), whether gamma-H2AX expression follows the pattern of proliferation of atypical squamous cells as shown by EGFR immunoreactivity, and whether it is correlated with clinicopathologic variables in ISCC. Immunostaining for both the factors was scored semiquantitatively for moderate and strong intensities. Gamma-H2AX and EGFR expression, respectively, increased from NE and CIN1 to CIN2/3 and ISCCs significantly (P=0.0001, respectively). Gamma-H2AX reactivity was found in the nuclei of the cells of the upper epithelial levels and the cells of basal/parabasal type in variable quantities in NE and CIN; expression of gamma-H2AX was seen in the nuclei of ISCC including keratinizing cells in horn pearls. EGFR staining was mainly membranous and noted in basal/parabasal cells in NE and atypically proliferating keratinocytes in CIN and nonkeratinizing cells of ISCC. In addition, immature squamous metaplasias were decorated by the antibodies used. Immunoscores for gamma-H2AX and EGFR, respectively, did not differ between International Federation of Gynecology and Obstetrics stages I and II, keratinizing and nonkeratinizing ISCC, and CIN2/3 and ISCC. However, expression patterns were different for both the factors, suggesting their involvement in different biological mechanisms, with regard to gamma-H2AX apart from proliferation. Overexpression of gamma-H2AX in CIN2/3 and ISCC of the uterine cervix reflects the neoplastic transformation of cervical squamous epithelia in reaction to increased DNA-damage and supports the classification of dysplasia into low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions.
机译：组蛋白γ-H2AX是活化的DNA损伤的标志物，在不同的癌症及其前体病变中过表达，表明在致癌性转化中起作用。表皮生长因子受体（EGFR）在多种上皮肿瘤中过表达。这项研究旨在确定是否从正常的鳞状上皮癌（NE，n = 33）到宫颈上皮内瘤变（CIN; CIN1，n = 9; CIN2 / 3， n = 33）和宫颈浸润性鳞状细胞癌（ISCC，n = 33），如EGFR免疫反应性所示，γ-H2AX表达是否遵循非典型鳞状细胞的增殖模式，以及是否与ISCC中的临床病理变量相关。对这两个因素的免疫染色均以中等强度和强强度进行半定量评分。 γ-H2AX和EGFR表达分别从NE和CIN1显着增加到CIN2 / 3和ISCC（分别为P = 0.0001）。在NE和CIN中，上皮水平的细胞核和基底/副基底型细胞的细胞核中发现了γ-H2AX反应性;在ISCC细胞核中观察到γ-H2AX的表达，包括角珍珠中的角化细胞。 EGFR染色主要是膜性的，在NE的基底/副基底细胞和CIN的非典型增生角质形成细胞以及ISCC的非角化细胞中可见。此外，未成熟的鳞状上皮化生被所用抗体修饰。国际妇产科联合会的I和II期，ISCC角化和非角化ISCC和CIN2 / 3和ISCC的gamma-H2AX和EGFR免疫分数没有差异。然而，对于这两个因素，表达模式是不同的，这表明除了增殖以外，就γ-H2AX而言，它们参与了不同的生物学机制。 γ-H2AX在子宫颈CIN2 / 3和ISCC中的过度表达反映了子宫颈鳞状上皮的赘生性转化，以应对DNA损伤增加，并支持将异型增生分类为低度鳞状上皮内病变和高度鳞状上皮内病变。

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