Piek J M J, Verheijen R H M, Menko F H, Jongsma A P M, Weegenaar J, Gille J J P, Pals G, Kenemans P, van Diest P J
Department of Obstetrics and Gynaecology, VU University Medical Centre, 1007 MB Amsterdam, the Netherlands.
Histopathology. 2003 Jul;43(1):26-32. doi: 10.1046/j.1365-2559.2003.01654.x.
To investigate the occurrence of preinvasive neoplastic lesions in ovarian surface epithelium and ovarian inclusion cyst epithelium of women with a hereditary predisposition to the development of female adnexal (ovarian and fallopian tube) carcinoma and to assess the expression of differentiation and proliferation related proteins within putative sites of origin of serous ovarian carcinoma, the ovarian surface epithelium and ovarian inclusion cyst epithelium.
Twenty-one ovaries, prophylactically removed from 11 women predisposed to the development of female adnexal cancer (cases) were compared with 22 ovaries from 11 women without such predisposition (controls). Archival histological specimens were screened for hyperplastic and dysplastic epithelial lesions. In both the ovarian surface and inclusion cyst epithelia, the percentage of cells was determined that stained positively for Ki67, p21, p27, p53, cyclin A, cyclin D1, bcl-2 and the presence of HER-2/neu, oestrogen (ER-alpha) and progesterone receptors (PR).
No preinvasive neoplastic lesions were detected. However, hyperplastic areas were found in three cases and in four controls (NS). ER-alpha (P = 0.013), PR (P < 0.001), bcl-2 (P = 0.008), p21 (P = 0.046) and p27 (P = 0.008) were expressed in a significantly higher percentage of cells in inclusion cyst epithelium than in ovarian surface epithelium (both groups). The latter showed higher bcl-2 expression in cases (P = 0.05) compared with controls. The inclusion cyst epithelium of cases showed higher expression of bcl-2 (P = 0.006) and PR (P = 0.039) compared with controls. Proliferation was low in both cases and controls as reflected by low Ki67 expression. Over-expression of p53, cyclin D1 and HER-2/neu was not detected.
Premalignant changes are not a common feature of ovaries removed prophylactically from women predisposed to the development of female adnexal carcinoma. Increased expression of p21, p27, and ER-alpha is seen in inclusion cyst compared with ovarian surface epithelium of women with and without an inherited risk of adnexal carcinoma. This is most probably caused by the different intraovarian hormonal milieu of inclusion cyst epithelium. However, the increased expression of bcl-2 and PR in the inclusion cyst epithelium of patients with a hereditary predisposition may reflect early disruption of hormonal balance and growth control.
研究具有遗传性女性附件（卵巢和输卵管）癌发病倾向的女性，其卵巢表面上皮和卵巢包涵囊肿上皮中癌前肿瘤性病变的发生情况，并评估浆液性卵巢癌假定起源部位（卵巢表面上皮和卵巢包涵囊肿上皮）中分化和增殖相关蛋白的表达。
将预防性切除的11名具有女性附件癌发病倾向女性（病例组）的21个卵巢，与11名无此发病倾向女性（对照组）的22个卵巢进行比较。对存档的组织学标本进行增生性和发育异常上皮病变筛查。在卵巢表面上皮和包涵囊肿上皮中，测定Ki67、p21、p27、p53、细胞周期蛋白A、细胞周期蛋白D1、bcl-2染色阳性的细胞百分比，以及HER-2/neu、雌激素（ER-α）和孕激素受体（PR）的存在情况。
未检测到癌前肿瘤性病变。然而，在3例病例和4例对照中发现了增生区域（无统计学差异）。与卵巢表面上皮（两组）相比，包涵囊肿上皮中ER-α（P = 0.013）、PR（P < 0.001）、bcl-2（P = 0.008）、p21（P = 0.046）和p27（P = 0.008）的阳性表达细胞百分比显著更高。病例组卵巢表面上皮的bcl-2表达高于对照组（P = 0.05）。病例组的包涵囊肿上皮与对照组相比，bcl-2（P = 0.006）和PR（P = 0.039）表达更高。Ki67表达低反映出病例组和对照组的增殖均较低。未检测到p53、细胞周期蛋白D1和HER-2/neu的过表达。
对于具有女性附件癌发病倾向的女性，预防性切除的卵巢中癌前病变并非常见特征。与有或无附件癌遗传风险女性的卵巢表面上皮相比，包涵囊肿中p21、p27和ER-α的表达增加。这很可能是由包涵囊肿上皮不同的卵巢内激素环境所致。然而，具有遗传易感性患者的包涵囊肿上皮中bcl-2和PR表达增加，可能反映了激素平衡和生长控制的早期破坏。
