Department of Pathology, Landesklinikum Thermenregion, Moedling, Austria.
Int J Gynecol Pathol. 2011 Jan;30(1):76-83. doi: 10.1097/PGP.0b013e3181eb2fcb.
The histone γ-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 γ-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 γ-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 γ-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 γ-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 γ-H2AX apart from proliferation. Overexpression of γ-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.
组蛋白 γ-H2AX 是一种活性 DNA 损伤的标志物，在不同的癌症及其前体病变中过度表达，表明其在致癌转化中起作用。表皮生长因子受体（EGFR）在多种上皮性肿瘤中过度表达。本研究旨在确定 γ-H2AX 的免疫组织化学表达是否参与从正常宫颈鳞状上皮（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）的形态谱的进展，γ-H2AX 表达是否遵循 EGFR 免疫反应性显示的非典型鳞状细胞的增殖模式，以及它是否与 ISCC 的临床病理变量相关。用半定量方法对两种因素的免疫染色进行评分，以评估中度和强强度。γ-H2AX 和 EGFR 的表达分别从 NE 和 CIN1 增加到 CIN2/3 和 ISCC（分别为 P=0.0001）。在 NE 和 CIN 中，γ-H2AX 反应性可在不同数量的上皮上层细胞和基底/副基底类型的细胞的核中发现；在包括角珠中的角化细胞在内的 ISCC 细胞的核中可见 γ-H2AX 的表达。EGFR 染色主要为膜性，在 NE 的基底/副基底细胞和 CIN 的非典型增殖的角质形成细胞以及非角化的 ISCC 细胞中可见。此外，不成熟的鳞状化生也被这些抗体所修饰。γ-H2AX 和 EGFR 的免疫评分在国际妇产科联合会（FIGO）分期 I 和 II、角化和非角化 ISCC 以及 CIN2/3 和 ISCC 之间没有差异。然而，两种因素的表达模式不同，表明它们涉及不同的生物学机制，除了增殖外，γ-H2AX 也参与其中。在子宫颈 CIN2/3 和 ISCC 中过度表达的 γ-H2AX 反映了宫颈鳞状上皮的肿瘤转化，以应对增加的 DNA 损伤，并支持将发育不良分为低级别鳞状上皮内病变和高级别鳞状上皮内病变。
