Körner Meike, Burckhardt Elisabeth, Mazzucchelli Luca
Institute of Pathology, University of Bern, Bern, Switzerland.
J Pathol. 2005 Sep;207(1):20-6. doi: 10.1002/path.1817.
Ovarian serous tumours may arise from the ovarian surface epithelium or from ovarian cortical epithelial inclusion cysts. However, little is known about the pathogenetic mechanisms involved in the progression from ovarian surface epithelium or inclusion cysts to neoplastic disease. In the present study, chromosomal aberrations typical of ovarian serous tumours were studied in ovarian surface epithelium and inclusion cysts. Ten ovaries with inclusion cysts obtained from patients without a gynaecological tumour, as well as 15 serous borderline tumours and 16 invasive high-grade serous carcinomas with inclusion cysts either in the ipsi- or in the contralateral ovary, were investigated by fluorescence in situ hybridization (FISH) using centromere enumeration probes directed against chromosomes 1, 6, 7, and X. The proportions of aneusomic cells were assessed. Trisomies 1 and 7 and monosomies 6 and X were present in the surface epithelium, inclusion cysts, and tumours, providing evidence for a link between the surface epithelium, and inclusion cysts, and serous neoplasia. Inclusion cysts generally harboured more aneusomic cells than the associated surface epithelium, suggesting an influence of the ovarian stroma on the development of chromosomal instability. Moreover, inclusion cysts associated with borderline tumours displayed a higher proportion of aneusomic cells than inclusion cysts associated with invasive high-grade carcinoma and than inclusion cysts in ovaries without neoplastic disease. These results suggest a genetic field defect of the inclusion cyst epithelium in serous borderline tumours. Invasive high-grade serous carcinomas, by contrast, may arise from single cell clones subject to a different set of genetic events.
卵巢浆液性肿瘤可能起源于卵巢表面上皮或卵巢皮质上皮包涵囊肿。然而，对于从卵巢表面上皮或包涵囊肿发展为肿瘤性疾病所涉及的发病机制知之甚少。在本研究中，对卵巢表面上皮和包涵囊肿中典型的卵巢浆液性肿瘤染色体畸变进行了研究。通过荧光原位杂交（FISH），使用针对1号、6号、7号和X染色体的着丝粒计数探针，对10例从无妇科肿瘤患者获取的带有包涵囊肿的卵巢、15例浆液性交界性肿瘤以及16例同侧或对侧卵巢带有包涵囊肿的浸润性高级别浆液性癌进行了研究。评估了非整倍体细胞的比例。1号和7号染色体三体以及6号和X染色体单体存在于表面上皮、包涵囊肿和肿瘤中，这为表面上皮、包涵囊肿与浆液性肿瘤之间的联系提供了证据。包涵囊肿通常比相关的表面上皮含有更多的非整倍体细胞，这表明卵巢间质对染色体不稳定性的发展有影响。此外，与交界性肿瘤相关的包涵囊肿显示出比与浸润性高级别癌相关的包涵囊肿以及无肿瘤疾病卵巢中的包涵囊肿更高比例的非整倍体细胞。这些结果提示浆液性交界性肿瘤中包涵囊肿上皮存在遗传场缺陷。相比之下，浸润性高级别浆液性癌可能起源于经历了不同遗传事件的单细胞克隆。
