Cheng Liang, Jones Timothy D, McCarthy Ryan P, Eble John N, Wang Mingsheng, MacLennan Gregory T, Lopez-Beltran Antonio, Yang Ximing J, Koch Michael O, Zhang Shaobo, Pan Chong-Xian, Baldridge Lee Ann
Department of Pathology and Laboratory Medicine, Indiana University Medical Center, University Hospital 3465, 550 North University Boulevard, Indianapolis, Indiana 46202, USA.
Am J Pathol. 2005 May;166(5):1533-9. doi: 10.1016/S0002-9440(10)62369-3.
In most cases, small-cell carcinoma of the urinary bladder is admixed with other histological types of bladder carcinoma. To understand the pathogenetic relationship between the two tumor types, we analyzed histologically distinct tumor cell populations from the same patient for loss of heterozygosity (LOH) and X chromosome inactivation (in female patients). We examined five polymorphic microsatellite markers located on chromosome 3p25-26 (D3S3050), chromosome 9p21 (IFNA and D9S171), chromosome 9q32-33 (D9S177), and chromosome 17p13 (TP53) in 20 patients with small-cell carcinoma of the urinary bladder and concurrent urothelial carcinoma. DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-assisted microdissection. A nearly identical pattern of allelic loss was observed in the two tumor types in all cases, with an overall frequency of allelic loss of 90% (18 of 20 cases). Three patients showed different allelic loss patterns in the two tumor types at a single locus; however, the LOH patterns at the remaining loci were identical. Similarly, the same pattern of nonrandom X chromosome inactivation was present in both carcinoma components in the four cases analyzed. Concordant genetic alterations and X chromosome inactivation between small-cell carcinoma and coexisting urothelial carcinoma suggest that both tumor components originate from the same cells in the urothelium.
在大多数情况下，膀胱小细胞癌与其他组织学类型的膀胱癌混合存在。为了解这两种肿瘤类型之间的致病关系，我们分析了同一患者组织学上不同的肿瘤细胞群体的杂合性缺失（LOH）和X染色体失活（女性患者）情况。我们检测了位于3号染色体p25 - 26区域（D3S3050）、9号染色体p21区域（IFNA和D9S171）、9号染色体q32 - 33区域（D9S177）以及17号染色体p13区域（TP53）的五个多态性微卫星标记，共检测了20例膀胱小细胞癌合并尿路上皮癌患者。使用激光辅助显微切割从福尔马林固定、石蜡包埋的组织切片中制备DNA样本。在所有病例中，两种肿瘤类型均观察到几乎相同的等位基因缺失模式，等位基因缺失的总体频率为90%（20例中的18例）。三名患者在单个位点的两种肿瘤类型中表现出不同的等位基因缺失模式；然而，其余位点的LOH模式相同。同样，在分析的四例病例中，两种癌成分均存在相同的非随机X染色体失活模式。膀胱小细胞癌与共存的尿路上皮癌之间一致的基因改变和X染色体失活表明，两种肿瘤成分均起源于尿路上皮中的同一细胞。
