Kanai M, Shiozawa T, Xin L, Nikaido T, Fujii S
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Asahi, Matsumoto, Japan.
Cancer. 1998 May 1;82(9):1709-19. doi: 10.1002/(sici)1097-0142(19980501)82:9<1709::aid-cncr18>3.0.co;2-8.
Malignant transformation of sex steroid-dependent tissues has been reported to be associated with abnormal expression of sex steroid receptors. In addition, abnormalities of cell cycle-related molecules have been demonstrated in various malignancies. However, expression of steroid receptors and cell cycle-related molecules in the process of malignant transformation of the ectocervical squamous epithelium, which also is a sex steroid-dependent tissue, has not been elucidated fully.
Immunohistochemical staining was performed on formalin fixed, paraffin embedded tissue sections of normal squamous epithelia (30 cases), cervical intraepithelial neoplasia (CIN) (21 cases), and invasive squamous carcinoma (SCC) (33 cases), using antibodies against estrogen receptors (ER), progesterone receptors (PR), cyclins (E, A, and B1), cyclin-dependent kinases (cdk2 and cdc2), and p53 protein. In addition, growth activity of SCC was evaluated by Ki-67 labeling.
In the normal epithelia, diffuse proportionate to regional expression of ER/PR and sporadic expression of cyclins/cdks were observed mainly in the parabasal cells irrespective of the menstrual cycle. In the neoplastic lesions, the expression of ER markedly decreased; however, the expression of PR increased. The expression of cyclins, cdks, and p53 was increased in a considerable number of these neoplastic cases. In addition, cyclin A positive SCC had elevated Ki-67 labeling, whereas cyclin E positive SCC cases had lower Ki-67 labeling.
These findings suggest that malignant transformation of ectocervical epithelia is associated with loss of normal growth control by steroid hormones as well as with the acquisition of abnormal cell cycle regulatory mechanisms.
据报道，性类固醇依赖组织的恶性转化与性类固醇受体的异常表达有关。此外，细胞周期相关分子的异常已在各种恶性肿瘤中得到证实。然而，宫颈外鳞状上皮作为一种性类固醇依赖组织，其恶性转化过程中类固醇受体和细胞周期相关分子的表达尚未完全阐明。
使用抗雌激素受体（ER）、孕激素受体（PR）、细胞周期蛋白（E、A和B1）、细胞周期蛋白依赖性激酶（cdk2和cdc2）以及p53蛋白的抗体，对30例正常鳞状上皮、21例宫颈上皮内瘤变（CIN）和33例浸润性鳞状细胞癌（SCC）的福尔马林固定、石蜡包埋组织切片进行免疫组织化学染色。此外，通过Ki-67标记评估SCC的生长活性。
在正常上皮中，无论月经周期如何，ER/PR的区域表达呈弥漫性比例，细胞周期蛋白/细胞周期蛋白依赖性激酶呈散在表达，主要见于基底旁细胞。在肿瘤病变中，ER的表达明显降低；然而，PR的表达增加。在相当数量的这些肿瘤病例中，细胞周期蛋白、细胞周期蛋白依赖性激酶和p53的表达增加。此外，细胞周期蛋白A阳性的SCC的Ki-67标记升高，而细胞周期蛋白E阳性的SCC病例的Ki-67标记较低。
这些发现表明，宫颈外上皮的恶性转化与类固醇激素对正常生长控制的丧失以及异常细胞周期调节机制的获得有关。
