Department of Pathology, Landesklinikum Thermenregion Moedling, Sr. Maria Restitutagasse 12, Moedling, Austria.
Int J Gynecol Pathol. 2011 Nov;30(6):583-90. doi: 10.1097/PGP.0b013e31821e18fd.
Survivin inhibits apoptosis and is involved in the regulation of cell cycle progression and in the mitotic spindle formation. It is overexpressed in many cancers. The histone γ-H2AX is a marker of activated DNA damage and is overexpressed in different cancers and their precursor lesions. It also forms early during apoptosis. Eighty-seven formalin-fixed, paraffin-embedded archival vulvar tissues originating from 55 preoperatively untreated patients were immunostained with antibodies to survivin and γ-H2AX to determine their expression in normal squamous vulvar epithelia (NE, n=25), lichen sclerosus (n=10), high-grade classic vulvar intraepithelial neoplasia (n=16), differentiated vulvar intraepithelial neoplasia (n=16), and vulvar invasive keratinizing squamous cell carcinoma (ISCC, n=20; FIGO Ib). Immunostaining for both factors was scored for moderate and strong intensities with regard to quantity. Statistical analysis was performed by the χ test and Fisher exact test. Nuclear surviving expression increased from NE and lichen scleros to high-grade classic vulvar intraepithelial neoplasia, differentiated vulvar intraepithelial neoplasia, and ISCC significantly (P=0.0001) and followed the distribution of immature squamous epithelial cells. Positive scores for γ-H2AX were found in nuclei of cells in all diagnostic cohorts, in any epithelial level with some accentuation in the upper layers, was seen in pycnotic nuclei in horn pearls of ISCC and apoptotic bodies, without relevant statistical distributions. Immunoscores did not differ between grade 1 and grades 2/3. Expression patterns were different for both factors, suggesting their involvement in different biologic mechanisms as an early event leading to resistance to apoptosis in vulvar carcinogenesis.
Survivin 抑制细胞凋亡，参与细胞周期进程的调控和有丝分裂纺锤体的形成。它在许多癌症中过度表达。组蛋白 γ-H2AX 是激活的 DNA 损伤的标志物，在不同的癌症及其前体病变中过度表达。它也在细胞凋亡早期形成。对 55 例未经术前治疗的患者的 87 例福尔马林固定、石蜡包埋的存档外阴组织进行了 survivin 和 γ-H2AX 抗体免疫染色，以确定它们在正常鳞状外阴上皮（NE，n=25）、硬化性苔藓（n=10）、高级别经典外阴上皮内瘤变（n=16）、分化的外阴上皮内瘤变（n=16）和外阴浸润性角化鳞状细胞癌（ISCC，n=20；FIGO Ib）中的表达。根据数量对两种因子的中度和强强度进行免疫染色评分。通过 χ 检验和 Fisher 确切检验进行统计学分析。核 survivin 表达从 NE 和硬化性苔藓增加到高级别经典外阴上皮内瘤变、分化的外阴上皮内瘤变和 ISCC，差异有统计学意义（P=0.0001），并随未成熟的鳞状上皮细胞分布而变化。γ-H2AX 的阳性评分见于所有诊断队列的细胞核，在任何上皮层均可见，在上层细胞中更为明显，在 ISCC 的角珠和凋亡小体的浓缩核中可见，无相关的统计学分布。1 级和 2/3 级之间的免疫评分无差异。两种因子的表达模式不同，表明它们参与不同的生物学机制，作为外阴癌发生中导致细胞凋亡抵抗的早期事件。
