Koi Chiho, Hachisuga Toru, Murakami Midori, Kurita Tomoko, Nguyen Thuy Thi, Shimajiri Shohei, Fujino Yoshihisa
From the Departments of 1Obstetrics and Gynecology, 2Pathology and Cell Biology, and 3Preventive Medicine and Community Health, School of Medicine, University of Occupational and Environmental Health, Iseigaoka, Yahatanishi-ku, Kitakyushu, Japan.
Menopause. 2015 Jan;22(1):104-7. doi: 10.1097/GME.0000000000000265.
The p53 signature, which (although morphologically unremarkable) displays diffuse and strong p53 nuclear staining, has been proposed to be a precursor of serous endometrial intraepithelial carcinoma. We examined the overexpression of p53 in postmenopausal endometrial glands.
Postmenopausal endometrial tissues of 82 women with benign disease, including 10 hormone users, were evaluated in this study. Tissues with endometrial hyperplasia and/or polyps were excluded based on a histopathologic review. Expressions of estrogen receptor-α, Ki-67, and p53 were immunohistochemically examined. Apoptotic cells were identified using a terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Overexpression of p53 was categorized as moderate to strong in more than 50% of glandular cell nuclei.
Focal glandular overexpression of p53 was observed in 1 (9%) of 10 and in 8 (11%) of 72 postmenopausal endometrial tissue specimens in women with and women without a history of hormone use, respectively. Among nonhormone users, the median Ki-67 and apoptotic indices in the postmenopausal endometrial glands of women with and women without overexpression of p53 were 16% and 6% (P = 0.007) and 1% and 1% (P = 0.345), respectively. All postmenopausal endometrial glands were positive for estrogen receptor-α, regardless of the overexpression of p53. The postmenopausal endometrial glands of estrogen users exhibited significantly higher Ki-67 and apoptotic indices than those of nonestrogen users (P = 0.001 and P < 0.001, respectively).
Overexpression of p53 may be responsible for the high proliferative activity of postmenopausal endometrial glandular cells associated with conditions of low apoptotic cell death.
p53特征（尽管形态上无明显异常）表现为弥漫性且强烈的p53核染色，已被认为是浆液性子宫内膜上皮内癌的前驱病变。我们检测了绝经后子宫内膜腺体中p53的过表达情况。
本研究评估了82例患有良性疾病的绝经后女性的子宫内膜组织，其中包括10例激素使用者。根据组织病理学检查结果，排除了存在子宫内膜增生和/或息肉的组织。采用免疫组织化学方法检测雌激素受体-α、Ki-67和p53的表达。使用末端脱氧核苷酸转移酶dUTP缺口末端标记法鉴定凋亡细胞。p53过表达定义为超过50%的腺细胞核呈中度至强阳性。
有激素使用史的女性中，10例绝经后子宫内膜组织标本中有1例（9%）出现p53局灶性腺体过表达；无激素使用史的女性中，72例绝经后子宫内膜组织标本中有8例（11%）出现p53局灶性腺体过表达。在非激素使用者中，p53过表达和未过表达的绝经后女性子宫内膜腺体中，Ki-67指数中位数分别为16%和6%（P = 0.007），凋亡指数中位数分别为1%和1%（P = 0.345）。无论p53是否过表达，所有绝经后子宫内膜腺体的雌激素受体-α均呈阳性。雌激素使用者的绝经后子宫内膜腺体的Ki-67指数和凋亡指数显著高于非雌激素使用者（分别为P = 0.001和P < 0.001）。
p53过表达可能是导致绝经后子宫内膜腺细胞增殖活性升高且凋亡细胞死亡减少的原因。
