Esteller M, García A, Martínez-Palones J M, Xercavins J, Reventós J
Centre d'Investigacions en Bioquímica i Biologia Molecular, Hospital Universitari Materno-Infantil Vall d'Herbrón, Barcelona, Spain.
Lab Invest. 1997 Jan;76(1):109-16.
Carcinoma of the endometrium is the most frequently diagnosed gynecologic malignancy in the western world. Because endometrial carcinoma is monoclonal in origin, the small samples obtained in endometrial pipelle biopsies can be used in PCR clonal studies to distinguish cancerous from noncancerous lesions. The method used for clonal analysis was based on RFLP of the X chromosome-linked phosphoglycerokinase gene and random inactivation of one X chromosome by methylation in women. Among 50 endometrial pipelle biopsies, 26 (52%) were found to be heterozygous for the above-mentioned polymorphism. Of the samples taken from these informative (ie, heterozygous) patients, six were monoclonal including five cases of endometrial carcinoma and one of endometrial atypical hyperplasia. In each case, the same pattern of monoclonality was present in the surgical specimen counterpart. All of the remaining samples were polyclonal and, when the anatomical pathology data were contrasted, they correlated with nonmalignant endometrium (five secretory, five proliferative, seven atrophic, and three simple hyperplasias). In addition, genetic alterations study of monoclonal endometrial samples revealed a K-ras point mutation and a c-erbB2/neu gene amplification in two different endometrial carcinomas. Both alterations were also detected in the surgical specimens. In addition, a diagnosed set of 10 samples of simple hyperplasia and 5 of atypical hyperplasia were subjected to clonal assay. Among eight informative cases, the three that showed that showed the monoclonal pattern corresponded with cases of atypical hyperplasia. No other genetic alterations were detected in these samples. In conclusion, our data indicate that the detection of clonality in endometrial biopsy samples obtained by pipelle would be a useful application for the early diagnosis of endometrial cancer.
子宫内膜癌是西方世界最常被诊断出的妇科恶性肿瘤。由于子宫内膜癌起源于单克隆，子宫内膜吸管活检获取的小样本可用于聚合酶链反应（PCR）克隆研究，以区分癌性病变和非癌性病变。用于克隆分析的方法基于X染色体连锁磷酸甘油激酶基因的限制性片段长度多态性（RFLP），以及女性中一条X染色体通过甲基化随机失活。在50例子宫内膜吸管活检样本中，26例（52%）被发现对上述多态性呈杂合状态。从这些信息丰富（即杂合）的患者身上获取的样本中，6例为单克隆，包括5例子宫内膜癌和1例子宫内膜非典型增生。在每种情况下，手术标本对应物中均呈现相同的单克隆模式。其余所有样本均为多克隆，当与解剖病理学数据对比时，它们与非恶性子宫内膜相关（5例分泌期、5例增殖期、7例萎缩期和3例单纯性增生）。此外，对单克隆子宫内膜样本的基因改变研究显示，在两种不同的子宫内膜癌中检测到K-ras点突变和c-erbB2/neu基因扩增。这两种改变在手术标本中也被检测到。此外，对一组诊断为单纯性增生的10个样本和非典型增生的5个样本进行了克隆分析。在8例信息丰富的病例中，显示单克隆模式的3例与非典型增生病例相对应。在这些样本中未检测到其他基因改变。总之，我们的数据表明，通过吸管获取的子宫内膜活检样本中克隆性的检测对于子宫内膜癌的早期诊断将是一种有用的应用。
