Muresu R, Sini M C, Cossu A, Tore S, Baldinu P, Manca A, Pisano M, Loddo C, Dessole S, Pintus A, Tanda F, Palmieri G
Istituto di Genetica delle Popolazioni, C.N.R., Alghero, Maria La Palma, Italy.
Eur J Cancer. 2002 Sep;38(13):1802-9. doi: 10.1016/s0959-8049(02)00152-1.
Defective DNA mismatch repair and nonfunctional mechanisms controlling the proper progression of the cell cycle have been proposed as being responsible for the genomic instability and accumulation of karyotypic alterations in endometrial cancer (EC). To assess whether numerical chromosomal anomalies (aneuploidy) and microsatellite instability (MSI) might be representative of distinctive tumour behaviour, paraffin-embedded tissue samples from 86 patients with sporadic EC were evaluated by both fluorescence in situ hybridisation (FISH) and microsatellite analysis, using free nuclei and genomic DNAs (respectively). Approximately one-third of the tumours analysed (24/74; 32%) exhibited MSI, whereas 38/86 (44%) of the EC samples displayed aneuploidy. The majority of the unstable cases (15/24; 63%) were from advanced-stage patients. Conversely, 23 (61%) out of the 38 tumours with aneuploidy were from early-stage patients. No apparent correlation was found between MSI and aneuploidy, whereas the immunohistochemical (IHC) analysis revealed that inactivation of the MLH1 mismatch repair gene may be involved in the majority of the MSI+ sporadic ECs. No genetic or cytogenetic alteration analysed here seems to add any significant predictive value to the stage of disease.
DNA错配修复缺陷以及控制细胞周期正常进程的功能失调机制被认为是子宫内膜癌（EC）基因组不稳定和核型改变积累的原因。为了评估染色体数目异常（非整倍体）和微卫星不稳定性（MSI）是否可能代表独特的肿瘤行为，我们分别使用游离细胞核和基因组DNA，通过荧光原位杂交（FISH）和微卫星分析对86例散发性EC患者的石蜡包埋组织样本进行了评估。分析的肿瘤中约三分之一（24/74；32%）表现出MSI，而86例EC样本中有38例（44%）显示非整倍体。大多数不稳定病例（15/24；63%）来自晚期患者。相反，38例非整倍体肿瘤中有23例（61%）来自早期患者。未发现MSI与非整倍体之间存在明显相关性，而免疫组织化学（IHC）分析显示，MLH1错配修复基因的失活可能与大多数MSI+散发性ECs有关。此处分析的任何遗传或细胞遗传学改变似乎都未为疾病分期增加任何显著的预测价值。
