Gabra H, Langdon S P, Watson J E, Hawkins R A, Cohen B B, Taylor L, Mackay J, Steel C M, Leonard R C, Smyth J F
Imperial Cancer Research Fund Medical Oncology Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU.
Clin Cancer Res. 1995 Sep;1(9):945-53.
Forty-seven epithelial ovarian cancers were analyzed for loss of heterozygosity (LOH) at D11S35 (11q22), close to the progesterone receptor (PR) gene, and for tumoral estrogen receptor (ER) and PR content. Thirty-eight of 47 tumors were informative, and, of these, 14 exhibited LOH. There was a significant association (P = 0.014) between D11S35 LOH and low tumoral PR content. For all informative tumors, there was no correlation between ER and PR; however, exclusion of tumors with LOH from the informative series revealed a linear correlation between tumoral ER and PR (P = 0.013), and established ER (P = 0.025) and PR (P = 0.05) content as significant factors in relation to patient survival. Patients with ER-rich tumors with D11S35 LOH had particularly poor survival compared with ER-rich, D11S35 heterozygous, no loss patients (P = 0.014). Analysis of the same tumors using two other microsatellites, D11S935 (11p13) and NM23 (17q22), showed no statistically significant relationships, although there were nonsignificant trends for the correlation of ER and PR expression in informative tumors without allele loss at these loci. We propose that genomic structural alteration at or close to the PR gene locus has biological and clinical sequelae in ovarian cancer.
对47例上皮性卵巢癌进行了分析,检测其11号染色体22区(11q22)上靠近孕激素受体(PR)基因的D11S35位点杂合性缺失(LOH)情况,以及肿瘤组织中雌激素受体(ER)和PR的含量。47例肿瘤中有38例信息充分,其中14例出现LOH。D11S35位点LOH与肿瘤组织低PR含量之间存在显著相关性(P = 0.014)。对于所有信息充分的肿瘤,ER与PR之间无相关性;然而,将信息充分的肿瘤系列中出现LOH的肿瘤排除后,发现肿瘤组织中ER与PR之间存在线性相关性(P = 0.013),并且确定ER含量(P = 0.025)和PR含量(P = 0.05)是与患者生存相关的重要因素。与富含ER、D11S35杂合且无缺失的患者相比,D11S35位点LOH且富含ER的肿瘤患者生存情况特别差(P = 0.014)。使用另外两个微卫星D11S935(11p13)和NM23(17q22)对相同肿瘤进行分析,未显示出统计学上的显著关系,尽管在这些位点无等位基因缺失的信息充分的肿瘤中,ER与PR表达的相关性有不显著的趋势。我们认为PR基因位点或其附近的基因组结构改变在卵巢癌中具有生物学和临床后果。