Niederacher D, An H X, Camrath S, Dominik S I, Göhring U J, Oertel A, Grass M, Hantschmann P, Lordnejad M R, Beckmann M W
Department of Gynaecology and Obstetrics, Heinrich-Heine-Universität, Düsseldorf, Germany.
Eur J Cancer. 1998 Oct;34(11):1770-6. doi: 10.1016/s0959-8049(98)00270-6.
Genetic alterations of tumour suppressor genes, for which loss of heterozygosity (LOH) is one mechanism of gene inactivation, are important steps in the development of endometrial cancer. To investigate the clinical relevance of LOH of BRCA1 (17q21), TP53 (17p13) and TCRD (14q11) in endometrial cancer, polymerase chain reaction (PCR)-based fluorescent DNA technology for the detection of microsatellite polymorphisms was applied. One hundred and thirteen archival endometrial cancer samples with matched normal tissues were examined. Allele loss at three loci were correlated with age, tumour size, lymph node status, metastases, stage, histological types, grade, expression of oestrogen receptor (ER) and progesterone receptor (PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy (HRT). LOH for BRCA1 was detected in 18.1%, of TP53 in 26.9%, and of TCRD in 26.3% of informative cases. LOH of BRCA1 correlated with medium grade, positive ER status, and family history of cancer; LOH of TP53 correlated with younger age, high grade, positive PgR status, and with tumours from patients without HRT; LOH of TCRD correlated only with family history of cancer. LOH at all three loci correlated only with grade and positive family history. Allele loss of one of the three tumour suppressor loci did not correlate with disease-free survival (DFS), but LOH of BRCA1 correlated significantly with decreased overall survival (OS). The latter, together with the correlation of LOH of BRCA1 locus with steroid hormone receptor expression, might give a hint to the potential involvement of the co-localised 17 beta-hydroxysteroid dehydrogenase (HSD) gene in the development of endometrial cancer.
肿瘤抑制基因的遗传改变是子宫内膜癌发生发展的重要步骤，杂合性缺失（LOH）是基因失活的一种机制。为了研究BRCA1（17q21）、TP53（17p13）和TCRD（14q11）基因杂合性缺失在子宫内膜癌中的临床相关性，应用了基于聚合酶链反应（PCR）的荧光DNA技术检测微卫星多态性。对113例存档的伴有配对正常组织的子宫内膜癌样本进行了检测。三个位点的等位基因缺失与年龄、肿瘤大小、淋巴结状态、转移情况、分期、组织学类型、分级、雌激素受体（ER）和孕激素受体（PgR）表达、癌症家族史、既往癌症或癌前病变史以及既往激素替代疗法（HRT）史相关。在有信息的病例中，BRCA1基因杂合性缺失的检出率为18.1%，TP53为26.9%，TCRD为26.3%。BRCA1基因杂合性缺失与中等分级、ER阳性状态和癌症家族史相关；TP53基因杂合性缺失与较年轻的年龄、高分级、PgR阳性状态以及未接受HRT患者的肿瘤相关；TCRD基因杂合性缺失仅与癌症家族史相关。所有三个位点的杂合性缺失仅与分级和阳性家族史相关。三个肿瘤抑制位点之一的等位基因缺失与无病生存期（DFS）无关，但BRCA1基因杂合性缺失与总生存期（OS）显著降低相关。后者，连同BRCA1位点杂合性缺失与类固醇激素受体表达的相关性，可能提示共定位的17β-羟类固醇脱氢酶（HSD）基因在子宫内膜癌发生发展中的潜在作用。
